BDBM162127 (S)-noradrenaline (+)-noradrenaline (+)-norepinephrine (S)-norepinephrine
DL-[7-3H]norepinephrine NOREPINEPHRINE BDBM35234 [3H]NE Noradrenaline,(+)
(R)-(-)-norepinephrine (R)-4-(2-amino-1-hydroxyethyl)-1,2-benzenediol BDBM50029051 CHEMBL1437 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol (R)-norepinephrine NOREPINEPHRINE (-)-noradrenaline (R)-noradrenaline (-)-norepinephrine (-)-arterenol
BDBM50027502 alpha-Methyl-(-)norepinephrine,(+/-) CHEMBL764 METHYLNORADRENALINE Aldoclor-150 4-(2-Amino-1-hydroxy-propyl)-benzene-1,2-diol alpha-Methyl-(+)norepinephrine,(+/-) Aldoclor-250 alpha-Methyl-(+/-)norepinephrine,(+/-)
- Sabatucci, JP; Mahaney, PE; Leiter, J; Johnston, G; Burroughs, K; Cosmi, S; Zhang, Y; Ho, D; Deecher, DC; Trybulski, E Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors. Bioorg Med Chem Lett 20: 2809-12 (2010)
- Wong, DT; Bymaster, FP; Mayle, DA; Reid, LR; Krushinski, JH; Robertson, DW LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology 8: 23-33 (1993)
- Deecher, DC; Beyer, CE; Johnston, G; Bray, J; Shah, S; Abou-Gharbia, M; Andree, TH Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 318: 657-65 (2006)
- Dreyfus, N; Myers, JK; Badescu, VO; de Frutos, O; de la Puente, ML; Ding, C; Filla, SA; Fynboe, K; Gernert, DL; Heinz, BA; Hemrick-Luecke, SK; Johnson, KW; Johnson, MP; L?pez, P; Love, PL; Martin, LJ; Masquelin, T; McCoy, MJ; Mendiola, J; Morrow, D; Muhlhauser, M; Pascual, G; Perun, TJ; Pfeifer, LA; Phebus, LA; Richards, SJ; Rinc?n, JA; Seest, EP; Shah, J; Shaojuan, J; Simmons, RM; Stephenson, GA; Tromiczak, EG; Thompson, LK; Walter, MW; Weber, WW; Zarrinmayeh, H; Thomas, CE; Joshi, E; Iyengar, S; Johansson, AM Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor. ACS Med Chem Lett 4: 560-4 (2013)
- Bymaster, FP; Beedle, EE; Findlay, J; Gallagher, PT; Krushinski, JH; Mitchell, S; Robertson, DW; Thompson, DC; Wallace, L; Wong, DT Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg Med Chem Lett 13: 4477-80 (2003)
- Pechulis, AD; Beck, JP; Curry, MA; Wolf, MA; Harms, AE; Xi, N; Opalka, C; Sweet, MP; Yang, Z; Vellekoop, AS; Klos, AM; Crocker, PJ; Hassler, C; Laws, M; Kitchen, DB; Smith, MA; Olson, RE; Liu, S; Molino, BF 4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors. Bioorg Med Chem Lett 22: 7219-22 (2012)
- Béïque, JC; Lavoie, N; de Montigny, C; Debonnel, G Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol 349: 129-32 (1998)
- Tamagnan, GD; Brenner, E; Alagille, D; Staley, JK; Haile, C; Koren, A; Early, M; Baldwin, RM; Tarazi, FI; Baldessarini, RJ; Jarkas, N; Goodman, MM; Seibyl, JP Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER. Bioorg Med Chem Lett 17: 533-7 (2007)
- Kortylewicz, ZP; Coulter, DW; Han, G; Baranowska-Kortylewicz, J Norepinephrine-Transporter-Targeted and DNA-Co-Targeted Theranostic Guanidines. J Med Chem 63: 2051-2073 (2020)
- Wong, DT; Threlkeld, PG; Best, KL; Bymaster, FP A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther 222: 61-5 (1982)
- Brown, DG; Bernstein, PR; Wu, Y; Urbanek, RA; Becker, CW; Throner, SR; Dembofsky, BT; Steelman, GB; Lazor, LA; Scott, CW; Wood, MW; Wesolowski, SS; Nugiel, DA; Koch, S; Yu, J; Pivonka, DE; Li, S; Thompson, C; Zacco, A; Elmore, CS; Schroeder, P; Liu, J; Hurley, CA; Ward, S; Hunt, HJ; Williams, K; McLaughlin, J; Hoesch, V; Sydserff, S; Maier, D; Aharony, D Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity. ACS Med Chem Lett 4: 46-51 (2013)
- Paczkowski, FA; Bryan-Lluka, LJ; Pörzgen, P; Brüss, M; Bönisch, H Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters. J Pharmacol Exp Ther 290: 761-7 (1999)
- Cases-Thomas, MJ; Masters, JJ; Walter, MW; Campbell, G; Haughton, L; Gallagher, PT; Dobson, DR; Mancuso, V; Bonnier, B; Giard, T; Defrance, T; Vanmarsenille, M; Ledgard, A; White, C; Ouwerkerk-Mahadevan, S; Brunelle, FJ; Dezutter, NA; Herbots, CA; Lienard, JY; Findlay, J; Hayhurst, L; Boot, J; Thompson, LK; Hemrick-Luecke, S Discovery of novel and selective tertiary alcohol containing inhibitors of the norepinephrine transporter. Bioorg Med Chem Lett 16: 2022-5 (2006)
- Zhang, A; Zhou, G; Rong, SB; Johnson, KM; Zhang, M; Kozikowski, AP Thiophene derivatives: a new series of potent norepinephrine and serotonin reuptake inhibitors. Bioorg Med Chem Lett 12: 993-5 (2002)
- Jesudason, CD; Baker, JE; Bryant, RD; Fisher, JW; Gaich, GA; He, MM; Kahl, SD; Kriauciunas, AV; Heiman, ML; Peters, MA; Rito, CJ; Satterwhite, JH; Tinsley, FC; Trankle, WG; Shuker, AJ Combination of a Beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor for the treatment of obesity. ACS Med Chem Lett 2: 583-586 (2011)
- Paudel, S; Cao, Y; Guo, S; An, B; Kim, KM; Cheon, SH Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors. Bioorg Med Chem 23: 6418-26 (2015)
- Wu, D; Pontillo, J; Ching, B; Hudson, S; Gao, Y; Fleck, BA; Gogas, K; Wade, WS Discovery of a potent, selective, and less flexible selective norepinephrine reuptake inhibitor (sNRI). Bioorg Med Chem Lett 18: 4224-7 (2008)
- Paudel, S; Acharya, S; Yoon, G; Kim, KM; Cheon, SH Exploration of substituted arylpiperazine-tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors. Bioorg Med Chem 24: 5546-5555 (2016)
- Tamiya, J; Dyck, B; Zhang, M; Phan, K; Fleck, BA; Aparicio, A; Jovic, F; Tran, JA; Vickers, T; Grey, J; Foster, AC; Chen, C Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors. Bioorg Med Chem Lett 18: 3328-32 (2008)
- Fensome, A; Goldberg, J; McComas, CC; Trybulski, EJ; Woodworth, RP; Deecher, DC; Whiteside, GT; Zhang, P Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores. Bioorg Med Chem Lett 20: 1555-8 (2010)
- Roggen, H; Kehler, J; Stensbøl, TB; Hansen, T Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters. Bioorg Med Chem Lett 17: 2834-7 (2007)
- Molino, BF; Liu, S; Guzzo, PR; Beck, JP Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin US Patent US9085531 (2015)
- Reitz, AB; Sonveaux, E; Rosenkranz, RP; Verlander, MS; Melmon, KL; Hoffman, BB; Akita, Y; Castagnoli, N; Goodman, M Conjugates of catecholamines. 5. Synthesis and beta-adrenergic activity of N-(aminoalkyl)norepinephrine derivatives. J Med Chem 28: 634-42 (1985)
- Rafferty, MF; Borchardt, RT; Grunewald, GL Directional probes of the hydrophobic component of the aromatic ring binding site of norepinephrine N-methyltransferase. J Med Chem 25: 1204-8 (1983)
- Karakus, OO; Godugu, K; Rajabi, M; Mousa, SA Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin ?v?3 Receptors in the Treatment of Neuroblastoma. J Med Chem 63: 7653-7662 (2020)
- Bannwart, LM; Carter, DS; Cai, HY; Choy, JC; Greenhouse, R; Jaime-Figueroa, S; Iyer, PS; Lin, CJ; Lee, EK; Lucas, MC; Lynch, SM; Madera, AM; Moore, A; Ozboya, K; Raptova, L; Roetz, R; Schoenfeld, RC; Stein, KA; Steiner, S; Villa, M; Weikert, RJ; Zhai, Y Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors. Bioorg Med Chem Lett 18: 6062-6 (2008)
- Mahaney, PE; Gavrin, LK; Trybulski, EJ; Stack, GP; Vu, TA; Cohn, ST; Ye, F; Belardi, JK; Santilli, AA; Sabatucci, JP; Leiter, J; Johnston, GH; Bray, JA; Burroughs, KD; Cosmi, SA; Leventhal, L; Koury, EJ; Zhang, Y; Mugford, CA; Ho, DM; Rosenzweig-Lipson, SJ; Platt, B; Smith, VA; Deecher, DC Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. J Med Chem 51: 4038-49 (2008)
- Paczkowski, FA; Sharpe, IA; Dutertre, S; Lewis, RJ chi-Conotoxin and tricyclic antidepressant interactions at the norepinephrine transporter define a new transporter model. J Biol Chem 282: 17837-44 (2007)
- Lovelace, ES; Armishaw, CJ; Colgrave, ML; Wahlstrom, ME; Alewood, PF; Daly, NL; Craik, DJ Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter. J Med Chem 49: 6561-8 (2006)
- Paudel, S; Acharya, S; Kim, KM; Cheon, SH Design, synthesis, and biological evaluation of arylpiperazine-benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities. Bioorg Med Chem 24: 2137-45 (2016)
- Davids, E; Zhang, K; Kula, NS; Tarazi, FI; Baldessarini, RJ Effects of norepinephrine and serotonin transporter inhibitors on hyperactivity induced by neonatal 6-hydroxydopamine lesioning in rats. J Pharmacol Exp Ther 301: 1097-102 (2002)
- Cashman, JR; Ghirmai, S Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression. Bioorg Med Chem 17: 6890-7 (2009)
- Boot, JR; Boulet, SL; Clark, BP; Cases-Thomas, MJ; Delhaye, L; Diker, K; Fairhurst, J; Findlay, J; Gallagher, PT; Gilmore, J; Harris, JR; Masters, JJ; Mitchell, SN; Naik, M; Simmonds, RG; Smith, SM; Richards, SJ; Timms, GH; Whatton, MA; Wolfe, CN; Wood, VA N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake. Bioorg Med Chem Lett 16: 2714-8 (2006)
- Codd, EE; Shank, RP; Schupsky, JJ; Raffa, RB Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther 274: 1263-70 (1995)
- Hudson, S; Kiankarimi, M; Eccles, W; Dwight, W; Mostofi, YS; Genicot, MJ; Fleck, BA; Gogas, K; Aparicio, A; Wang, H; Wen, J; Wade, WS Structure-activity relationships of chiral selective norepinephrine reuptake inhibitors (sNRI) with increased oxidative stability. Bioorg Med Chem Lett 18: 4491-4 (2008)
- Vickers, T; Dyck, B; Tamiya, J; Zhang, M; Jovic, F; Grey, J; Fleck, BA; Aparicio, A; Johns, M; Jin, L; Tang, H; Foster, AC; Chen, C Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors. Bioorg Med Chem Lett 18: 3230-5 (2008)
- Xu, L; Izenwasser, S; Katz, JL; Kopajtic, T; Klein-Stevens, C; Zhu, N; Lomenzo, SA; Winfield, L; Trudell, ML Synthesis and biological evaluation of 2-substituted 3beta-tolyltropane derivatives at dopamine, serotonin, and norepinephrine transporters. J Med Chem 45: 1203-10 (2002)
- Hudson, S; Kiankarimi, M; Eccles, W; Mostofi, YS; Genicot, MJ; Dwight, W; Fleck, BA; Gogas, K; Wade, WS Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint. Bioorg Med Chem Lett 18: 4495-8 (2008)
- Pontillo, J; Wu, D; Ching, B; Hudson, S; Genicot, MJ; Gao, Y; Ewing, T; Fleck, BA; Gogas, K; Aparicio, A; Wang, H; Wen, J; Wade, WS Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with improved pharmaceutical characteristics. Bioorg Med Chem Lett 18: 6151-5 (2008)
- Zeng, F; Jarkas, N; Stehouwer, JS; Voll, RJ; Owens, MJ; Kilts, CD; Nemeroff, CB; Goodman, MM Synthesis, in vitro characterization, and radiolabeling of reboxetine analogs as potential PET radioligands for imaging the norepinephrine transporter. Bioorg Med Chem 16: 783-93 (2008)
- Brust, A; Palant, E; Croker, DE; Colless, B; Drinkwater, R; Patterson, B; Schroeder, CI; Wilson, D; Nielsen, CK; Smith, MT; Alewood, D; Alewood, PF; Lewis, RJ chi-Conopeptide pharmacophore development: toward a novel class of norepinephrine transporter inhibitor (Xen2174) for pain. J Med Chem 52: 6991-7002 (2009)
- Guzzo, PR; Liu, S; Ryan, KN; Molino, BF; DeOrazio, R; Olson, RE; Macor, JE 2,5-methano- and 2,5-ethano-tetrahydrobenzazepine derivatives and use thereof to block reuptake of norepinephrine, dopamine, and serotonin US Patent US9045468 (2015)
- Vu, AT; Cohn, ST; Terefenko, EA; Moore, WJ; Zhang, P; Mahaney, PE; Trybulski, EJ; Goljer, I; Dooley, R; Bray, JA; Johnston, GH; Leiter, J; Deecher, DC 3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors. Bioorg Med Chem Lett 19: 2464-7 (2009)
- Bøgesø, KP; Christensen, AV; Hyttel, J; Liljefors, T 3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake. J Med Chem 28: 1817-28 (1986)
- D?az, JL; Cuevas, F; Pazos, G; ?lvarez-Bercedo, P; Oliva, AI; Sarmentero, M?; Font, D; Jim?nez-Aquino, A; Mor?n, M; Port, A; Pascual, R; Dordal, A; Portillo-Salido, E; Reinoso, RF; Vela, JM; Almansa, C Bicyclic Diazepinones as Dual Ligands of the ?2?-1 Subunit of Voltage-Gated Calcium Channels and the Norepinephrine Transporter. J Med Chem 64: 2167-2185 (2021)
- Jin, C; Navarro, HA; Carroll, FI Development of 3-phenyltropane analogues with high affinity for the dopamine and serotonin transporters and low affinity for the norepinephrine transporter. J Med Chem 51: 8048-56 (2008)
- Maryanoff, BE; McComsey, DF; Castanzo, MJ; Setler, PE; Gardocki, JF; Shank, RP; Schneider, CR Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin. J Med Chem 27: 943-6 (1984)
- Tosh, DK; Janowsky, A; Eshleman, AJ; Warnick, E; Gao, ZG; Chen, Z; Gizewski, E; Auchampach, JA; Salvemini, D; Jacobson, KA Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters. J Med Chem 60: 3109-3123 (2017)
- Zeng, F; Stehouwer, JS; Jarkas, N; Voll, RJ; Williams, L; Camp, VM; Votaw, JR; Owens, MJ; Kilts, CD; Nemeroff, CB; Goodman, MM Synthesis and biological evaluation of 2beta,3alpha-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents. Bioorg Med Chem Lett 17: 3044-7 (2007)
- Beadle, CD; Boot, J; Camp, NP; Dezutter, N; Findlay, J; Hayhurst, L; Masters, JJ; Penariol, R; Walter, MW 1-Aryl-3,4-dihydro-1H-quinolin-2-one derivatives, novel and selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett 15: 4432-7 (2005)
- Rothman, RB; Baumann, MH; Dersch, CM; Romero, DV; Rice, KC; Carroll, FI; Partilla, JS Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39: 32-41 (2001)
- Shao, L; Hewitt, MC; Wang, F; Malcolm, SC; Ma, J; Campbell, JE; Campbell, UC; Engel, SR; Spicer, NA; Hardy, LW; Schreiber, R; Spear, KL; Varney, MA Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor. Bioorg Med Chem Lett 21: 1434-7 (2011)
- Shao, L; Hewitt, MC; Wang, F; Malcolm, SC; Ma, J; Campbell, JE; Campbell, UC; Engel, SR; Spicer, NA; Hardy, LW; Schreiber, R; Spear, KL; Varney, MA Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor. Bioorg Med Chem Lett 21: 1438-41 (2011)
- White, JD; Juniku, R; Huang, K; Yang, J; Wong, DT Synthesis of 1,1-[1-naphthyloxy-2-thiophenyl]-2-methylaminomethylcyclopropanes and their evaluation as inhibitors of serotonin, norepinephrine, and dopamine transporters. J Med Chem 52: 5872-9 (2009)
- Schou, M; Pike, VW; Sóvágó, J; Gulyás, B; Gallagher, PT; Dobson, DR; Walter, MW; Rudyk, H; Farde, L; Halldin, C Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET. Bioorg Med Chem 15: 616-25 (2006)
- Vu, AT; Cohn, ST; Zhang, P; Kim, CY; Mahaney, PE; Bray, JA; Johnston, GH; Koury, EJ; Cosmi, SA; Deecher, DC; Smith, VA; Harrison, JE; Leventhal, L; Whiteside, GT; Kennedy, JD; Trybulski, EJ 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors. J Med Chem 53: 2051-62 (2010)
- Blough, BE; Holmquist, CR; Abraham, P; Kuhar, MJ; Carroll, FI 3alpha-(4-Substituted phenyl)nortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter. Bioorg Med Chem Lett 10: 2445-7 (2001)
- Dounay, AB; Barta, NS; Campbell, BM; Coleman, C; Collantes, EM; Denny, L; Dutta, S; Gray, DL; Hou, D; Iyer, R; Maiti, SN; Ortwine, DF; Probert, A; Stratman, NC; Subedi, R; Whisman, T; Xu, W; Zoski, K Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists. Bioorg Med Chem Lett 20: 1114-7 (2010)
- Kalkman, HO; Subramanian, N; Hoyer, D Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders. Neuropsychopharmacology 25: 904-14 (2001)
- Rafferty, MF; Krass, P; Borchardt, RT; Grunewald, GL Importance of the aromatic ring in adrenergic amines. 8. 2-(Aminomethyl)-trans-2-decalols as inhibitors of norepinephrine N-methyltransferase. J Med Chem 25: 1250-2 (1983)
- Rothman, RB; Vu, N; Partilla, JS; Roth, BL; Hufeisen, SJ; Compton-Toth, BA; Birkes, J; Young, R; Glennon, RA In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J Pharmacol Exp Ther 307: 138-45 (2003)
- Bymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 27: 699-711 (2002)
- Dyck, B; Tamiya, J; Jovic, F; Pick, RR; Bradbury, MJ; O'Brien, J; Wen, J; Johns, M; Madan, A; Fleck, BA; Foster, AC; Li, B; Zhang, M; Tran, JA; Vickers, T; Grey, J; Saunders, J; Chen, C Characterization of thien-2-yl 1S,2R-milnacipran analogues as potent norepinephrine/serotonin transporter inhibitors for the treatment of neuropathic pain. J Med Chem 51: 7265-72 (2009)
- Bymaster, FP; Dreshfield-Ahmad, LJ; Threlkeld, PG; Shaw, JL; Thompson, L; Nelson, DL; Hemrick-Luecke, SK; Wong, DT Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 25: 871-80 (2001)
- Pettersson, M; Campbell, BM; Dounay, AB; Gray, DL; Xie, L; O'Donnell, CJ; Stratman, NC; Zoski, K; Drummond, E; Bora, G; Probert, A; Whisman, T Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine derivatives as dual norepinephrine reuptake inhibitors and 5-HT(1A) partial agonists. Bioorg Med Chem Lett 21: 865-8 (2011)
- Gray, DL; Xu, W; Campbell, BM; Dounay, AB; Barta, N; Boroski, S; Denny, L; Evans, L; Stratman, N; Probert, A Discovery and pharmacological characterization of aryl piperazine and piperidine ethers as dual acting norepinephrine reuptake inhibitors and 5-HT1A partial agonists. Bioorg Med Chem Lett 19: 6604-7 (2009)
- Zhou, J; Kläss, T; Johnson, KM; Giberson, KM; Kozikowski, AP Discovery of novel conformationally constrained tropane-based biaryl and arylacetylene ligands as potent and selective norepinephrine transporter inhibitors and potential antidepressants. Bioorg Med Chem Lett 15: 2461-5 (2005)
- Rafferty, MF; Wilson, DS; Monn, JA; Krass, P; Borchardt, RT; Grunewald, GL Importance of the aromatic ring in adrenergic amines. 7. Comparison of the stereoselectivity of norepinephrine N-methyltransferase for aromatic vs. nonaromatic substrates and inhibitors. J Med Chem 25: 1198-204 (1983)
- Grunewald, GL; Monn, JA; Rafferty, MF; Borchardt, RT; Krass, P Probes of the active site of norepinephrine N-methyltransferase: effect of hydrophobic and hydrophilic interactions on side-chain binding of amphetamine and alpha-methylbenzylamine. J Med Chem 25: 1248-50 (1983)
- McComas, CC; Vu, AT; Mahaney, PE; Cohn, ST; Fensome, A; Marella, MA; Nogle, L; Trybulski, EJ; Ye, F; Zhang, P; Alfinito, P; Bray, J; Johnston, G; Koury, E; Deecher, DC Synthesis and activity of 1-(3-amino-1-phenylpropyl)indolin-2-ones: a new class of selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett 18: 4929-31 (2008)
- Lee, KH; Park, CE; Min, KH; Shin, YJ; Chung, CM; Kim, HH; Yoon, HJ; Won-Kim, na; Ryu, EJ; Shin, YJ; Nam, HS; Cho, JW; Lee, HY Synthesis and pharmacological evaluation of 3-aryl-3-azolylpropan-1-amines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors. Bioorg Med Chem Lett 20: 5567-71 (2010)
- Van Orden, LJ; Van Dyke, PM; Saito, DR; Church, TJ; Chang, R; Smith, JA; Martin, WJ; Jaw-Tsai, S; Stangeland, EL A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure-activity relationships. Bioorg Med Chem Lett 23: 1456-61 (2013)
- Zhou, J; Kläss, T; Zhang, A; Johnson, KM; Wang, CZ; Ye, Y; Kozikowski, AP Synthesis and pharmacological evaluation of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes: thiophene analogues as potent norepinephrine transporter inhibitors. Bioorg Med Chem Lett 13: 3565-9 (2003)
- Zhou, J; Zhang, A; Kläss, T; Johnson, KM; Wang, CZ; Ye, YP; Kozikowski, AP Biaryl analogues of conformationally constrained tricyclic tropanes as potent and selective norepinephrine reuptake inhibitors: synthesis and evaluation of their uptake inhibition at monoamine transporter sites. J Med Chem 46: 1997-2007 (2003)
- Hoepping, A; Johnson, KM; George, C; Flippen-Anderson, J; Kozikowski, AP Novel conformationally constrained tropane analogues by 6-endo-trig radical cyclization and stille coupling - switch of activity toward the serotonin and/or norepinephrine transporter. J Med Chem 43: 2064-71 (2000)
- Millan, MJ; Gobert, A; Lejeune, F; Newman-Tancredi, A; Rivet, JM; Auclair, A; Peglion, JL S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther 298: 565-80 (2001)
- Carroll, FI; Tyagi, S; Blough, BE; Kuhar, MJ; Navarro, HA Synthesis and monoamine transporter binding properties of 3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters. Norepinephrine transporter selective compounds. J Med Chem 48: 3852-7 (2005)
- Del Bello, F; Sakloth, F; Partilla, JS; Baumann, MH; Glennon, RA Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine. Bioorg Med Chem 23: 5574-9 (2015)
- O'Neill, DJ; Adedoyin, A; Bray, JA; Deecher, DC; Fensome, A; Goldberg, JA; Harrison, J; Leventhal, L; Mann, C; Mark, L; Nogle, L; Sullivan, NR; Spangler, TB; Terefenko, EA; Trybulski, EJ; Uveges, AJ; Vu, A; Whiteside, GT; Zhang, P Discovery of novel selective norepinephrine inhibitors: 1-(2-morpholin-2-ylethyl)-3-aryl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxides (WYE-114152). J Med Chem 54: 6824-31 (2011)
- Heffernan, GD; Coghlan, RD; Manas, ES; McDevitt, RE; Li, Y; Mahaney, PE; Robichaud, AJ; Huselton, C; Alfinito, P; Bray, JA; Cosmi, SA; Johnston, GH; Kenney, T; Koury, E; Winneker, RC; Deecher, DC; Trybulski, EJ Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles. Bioorg Med Chem 17: 7802-15 (2009)
- Zhang, P; Terefenko, EA; McComas, CC; Mahaney, PE; Vu, A; Trybulski, E; Koury, E; Johnston, G; Bray, J; Deecher, D Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett 18: 6067-70 (2008)
- Zeng, F; Mun, J; Jarkas, N; Stehouwer, JS; Voll, RJ; Tamagnan, GD; Howell, L; Votaw, JR; Kilts, CD; Nemeroff, CB; Goodman, MM Synthesis, radiosynthesis, and biological evaluation of carbon-11 and fluorine-18 labeled reboxetine analogues: potential positron emission tomography radioligands for in vivo imaging of the norepinephrine transporter. J Med Chem 52: 62-73 (2009)
- Carlier, PR; Lo, MM; Lo, PC; Richelson, E; Tatsumi, M; Reynolds, IJ; Sharma, TA Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett 8: 487-92 (1999)
- Zhang, P; Terefenko, EA; Bray, J; Deecher, D; Fensome, A; Harrison, J; Kim, C; Koury, E; Mark, L; McComas, CC; Mugford, CA; Trybulski, EJ; Vu, AT; Whiteside, GT; Mahaney, PE 1- or 3-(3-Amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones: potent, selective, and orally efficacious norepinephrine reuptake inhibitors. J Med Chem 52: 5703-11 (2009)
- Carroll, FI; Gray, JL; Abraham, P; Kuzemko, MA; Lewin, AH; Boja, JW; Kuhar, MJ 3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogues of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters. J Med Chem 36: 2886-90 (1993)
- Zhang, S; Zhen, J; Reith, ME; Dutta, AK Discovery of novel trisubstituted asymmetric derivatives of (2S,4R,5R)-2-benzhydryl-5-benzylaminotetrahydropyran-4-ol, exhibiting high affinity for serotonin and norepinephrine transporters in a stereospecific manner. J Med Chem 48: 4962-71 (2005)
- Mladenova, G; Annedi, SC; Ramnauth, J; Maddaford, SP; Rakhit, S; Andrews, JS; Zhang, D; Porreca, F First-in-class, dual-action, 3,5-disubstituted indole derivatives having human nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI) activity for the treatment of neuropathic pain. J Med Chem 55: 3488-501 (2012)
- Boja, JW; Kuhar, MJ; Kopajtic, T; Yang, E; Abraham, P; Lewin, AH; Carroll, FI Secondary amine analogues of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters and N-norcocaine exhibit enhanced affinity for serotonin and norepinephrine transporters. J Med Chem 37: 1220-3 (1994)
- Orjales, A; Mosquera, R; Toledo, A; Pumar, MC; García, N; Cortizo, L; Labeaga, L; Innerárity, A Syntheses and binding studies of new [(aryl)(aryloxy)methyl]piperidine derivatives and related compounds as potential antidepressant drugs with high affinity for serotonin (5-HT) and norepinephrine (NE) transporters. J Med Chem 46: 5512-32 (2003)
- O'Neill, DJ; Adedoyin, A; Alfinito, PD; Bray, JA; Cosmi, S; Deecher, DC; Fensome, A; Harrison, J; Leventhal, L; Mann, C; McComas, CC; Sullivan, NR; Spangler, TB; Uveges, AJ; Trybulski, EJ; Whiteside, GT; Zhang, P Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231). J Med Chem 53: 4511-21 (2010)
- Santra, S; Sharma, H; Vedachalam, S; Antonio, T; Reith, M; Dutta, A Development of potent dopamine-norepinephrine uptake inhibitors (DNRIs) based on a (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol molecular template. Bioorg Med Chem 23: 821-8 (2015)
- Mishra, M; Kolhatkar, R; Zhen, J; Parrington, I; Reith, ME; Dutta, AK Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: interaction with dopamine, serotonin, and norepinephrine transporters. Bioorg Med Chem 16: 2769-78 (2008)
- He, R; Kurome, T; Giberson, KM; Johnson, KM; Kozikowski, AP Further structure-activity relationship studies of piperidine-based monoamine transporter inhibitors: effects of piperidine ring stereochemistry on potency. Identification of norepinephrine transporter selective ligands and broad-spectrum transporter inhibitors. J Med Chem 48: 7970-9 (2005)
- Altenbach, RJ; Black, LA; Strakhova, MI; Manelli, AM; Carr, TL; Marsh, KC; Wetter, JM; Wensink, EJ; Hsieh, GC; Honore, P; Garrison, TR; Brioni, JD; Cowart, MD Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain. J Med Chem 53: 7869-73 (2010)
- Bartolomé, JM; Alcudia, A; Andrés, JI; Cid, JM; García, M; Megens, A; Toledo, MA; Trabanco, AA Novel 2-N,N-dimethylaminomethyl-2,3,3a,12b-tetrahydrodibenzo[b,f]furo[2,3-d]oxepin derivatives displaying combined norepinephrine reuptake inhibition and 5-HT2A/2C receptor antagonism. Bioorg Med Chem Lett 15: 2898-901 (2005)
- ChEMBL_582829 Inhibition of [3H]norepinephrine reuptake at norepinephrine transporter
- ChEMBL_144991 Inhibition of [3H]norepinephrine uptake at the rat norepinephrine transporter.
- ChEMBL_487427 Inhibition of norepinephrine uptake at rat brain norepinephrine transporter
- ChEBML_142964 Norepinephrine transporter activity was determined by the ability of compound to inhibit the neurotransmitter norepinephrine-NE reuptake system using [3H]norepinephrine as radioligand
- ChEMBL_142964 Norepinephrine transporter activity was determined by the ability of compound to inhibit the neurotransmitter norepinephrine-NE reuptake system using [3H]norepinephrine as radioligand
- ChEBML_143137 Compound was tested for its ability to inhibit the uptake of Norepinephrine in Norepinephrine transporter system
- ChEMBL_144966 Inhibition of Norepinephrine (NA) reuptake using cloned human Norepinephrine transporter was determined
- ChEMBL_1615835 Inhibition of norepinephrine transporter (unknown origin) assessed as suppression of synaptosomal uptake of norepinephrine
- ChEMBL_306535 Inhibition of [3H]norepinephrine uptake in HEK293 cells expressing human norepinephrine transporter
- ChEMBL_487422 Inhibition of norepinephrine uptake at human norepinephrine transporter expressed in MDCK-Net6 cells
- ChEMBL_608767 Inhibition of [3H]norepinephrine reuptake at rat brain frontal cortex norepinephrine transporter
- ChEMBL_142620 Selectivity for norepinephrine transporter
- ChEMBL_30253 Evaluated for norepinephrine as agonist.
- ChEMBL_30398 Evaluated for norepinephrine as agonist.
- ChEMBL_30399 Evaluated for norepinephrine as agonist.
- ChEMBL_333146 Inhibition of reuptake of Norepinephrine
- ChEMBL_495766 Inhibition of norepinephrine transporter
- ChEMBL_761553 Inhibition of norepinephrine transporter
- ChEBML_177242 Inhibition of norepinephrine uptake in synaptosomal preparation fro rat hypothalamus, using [3H]norepinephrine
- ChEMBL_142949 Compound was tested for the ability to inhibit [3H]norepinephrine binding to Norepinephrine transporter in rat synaptosomes
- ChEMBL_142950 Compound was tested for the ability to inhibit [3H]norepinephrine binding to Norepinephrine transporter in rat synaptosomes
- ChEMBL_177242 Inhibition of norepinephrine uptake in synaptosomal preparation fro rat hypothalamus, using [3H]norepinephrine
- ChEBML_142643 Ability to inhibit reuptake of norepinephrine ([3H]NE) at norepinephrine transporter of rat parietal/occipital region
- ChEMBL_142643 Ability to inhibit reuptake of norepinephrine ([3H]NE) at norepinephrine transporter of rat parietal/occipital region
- ChEMBL_458982 Binding affinity to norepinephrine transporter
- ChEMBL_520036 Binding affinity to norepinephrine transporter
- ChEMBL_539366 Binding affinity to norepinephrine transporter
- ChEMBL_806656 Inhibition of human norepinephrine transporter
- ChEMBL_818589 Binding affinity to norepinephrine transporter
- ChEBML_142803 The compound was tested for inhibition of [3H]norepinephrine uptake in HEK cells by expressing cDNA for human norepinephrine transporter
- ChEMBL_142803 The compound was tested for inhibition of [3H]norepinephrine uptake in HEK cells by expressing cDNA for human norepinephrine transporter
- ChEMBL_142801 Binding affinity against norepinephrine transporter
- ChEMBL_143118 Evaluated for the Competitive inhibition of uptake of norepinephrine
- ChEMBL_2162544 Inhibition of norepinephrine transporter (unknown origin)
- ChEMBL_320846 Inhibition of monoamine reuptake at norepinephrine transporter
- ChEMBL_321161 Inhibition constant against norepinephrine transporter
- ChEMBL_464100 Inhibition of NET mediated norepinephrine uptake
- ChEMBL_699574 Inhibition of human recombinant norepinephrine transporter
- ChEMBL_726927 Inhibition of human recombinant Norepinephrine transporter
- ChEMBL_761643 Inhibition of recombinant human norepinephrine transporter
- ChEBML_142625 Inhibition of [3H]mazindol binding to Norepinephrine transporter
- ChEBML_184434 Inhibition of norepinephrine (NE) into rat brain synaptosomes
- ChEMBL_142625 Inhibition of [3H]mazindol binding to Norepinephrine transporter
- ChEMBL_142627 Inhibition of [3H]- nisoxatine binding to Norepinephrine transporter
- ChEMBL_142638 Inhibition of reuptake of [3H]-NE at Norepinephrine transporter
- ChEMBL_142775 Compound was tested for the inhibition of norepinephrine (NE) reuptake
- ChEMBL_142778 Displacement of [3H]-Nisoxetine from norepinephrine transporter
- ChEMBL_142937 In vitro binding affinity on cloned Norepinephrine transporter
- ChEMBL_143119 Evaluated for the Non competitive inhibition of uptake of norepinephrine
- ChEMBL_143141 Compound was evaluated for binding to Norepinephrine Transporter (NET).
- ChEMBL_144981 Inhibition of [3H]nisoxetine binding at norepinephrine transporter
- ChEMBL_1525555 Binding affinity to norepinephrine transporter (unknown origin)
- ChEMBL_184434 Inhibition of norepinephrine (NE) into rat brain synaptosomes
- ChEMBL_320813 Binding inhibition towards human norepinephrine transporter
- ChEMBL_486188 Displacement of [3H]DMI from norepinephrine transporter
- ChEMBL_491871 Inhibition of norepinephrine uptake at human cloned NET
- ChEMBL_556594 Displacement of [3H]nisoxetine from norepinephrine transporter
- ChEMBL_658576 Binding affinity to human recombinant norepinephrine transporter
- ChEMBL_807238 Inhibition of rat NET-mediated norepinephrine reuptake
- ChEMBL_824331 Inhibition of rat NET-mediated norepinephrine reuptake
- Norepinephrine Uptake Assay (IC50) IC50 Values were obtained from inhibition of norepinephrine uptake in MDCK-Net6 cells, stably transfected with the human NET.
- ChEBML_131452 Tested in vitro for norepinephrine (NE) neuronal uptake inhibition
- ChEBML_142612 Inhibition of [3H]nisoxetine binding to norepinephrine (NE) transporter
- ChEBML_142956 Inhibition of Norepinephrine uptake from rat diencephalon-midbrain
- ChEBML_193336 Inhibition of uptake of tritiated norepinephrine (NE) in rat synaptosomes
- ChEMBL_131452 Tested in vitro for norepinephrine (NE) neuronal uptake inhibition
- ChEMBL_142609 Ability to inhibit the reuptake of NE at human norepinephrine transporter
- ChEMBL_142948 Binding potency for Norepinephrine transporter using [3H]NE
- ChEMBL_142957 Inhibition of [3H]nisoxetine binding to norepinephrine (NE) transporter
- ChEMBL_144980 Inhibition of [3H]nisoxetine binding at norepinephrine transporter was determined
- ChEMBL_144992 Inhibition of [3H]nisoxetine binding at norepinephrine transporter was determined
- ChEMBL_144993 Affinity for norepinephrine transporter determined by [3H]nisoxetine displacement.
- ChEMBL_1803913 Inhibition of [3H]norepinephrine uptake at NET (unknown origin)
- ChEMBL_193336 Inhibition of uptake of tritiated norepinephrine (NE) in rat synaptosomes
- ChEMBL_302810 Inhibition of [3H]-nisoxetine binding to rat norepinephrine transporter
- ChEMBL_303056 Inhibition of [3H]nisoxetine binding to rat Norepinephrine transporter
- ChEMBL_320832 In vitro binding affinity towards human norepinephrine transporter
- ChEMBL_357806 Binding affinity to norepinephrine transporter by radioligand binding assay
- ChEMBL_491868 Inhibition of norepinephrine uptake at NET in rat brain synaptosome
- ChEBML_142629 In vitro inhibition of [3H]norepinephrine uptake in rat brain synaptosomes
- ChEBML_143113 Binding affinity to norepinephrine (NE) transporter in rat forebrain tissue
- ChEBML_177401 Inhibition of uptake of tritiated norepinephrine (NE) into rat brain synaptosomes
- ChEMBL_1344246 Inhibition of NET-mediated norepinephrine uptake in rat brain synaptosomes
- ChEMBL_140759 In vitro inhibition of [3H]norepinephrine uptake in rat brain synaptosomes
- ChEMBL_140884 Binding affinity for norepinephrine transporter (NET) labeled with [3H]nisoxetine
- ChEMBL_142629 In vitro inhibition of [3H]norepinephrine uptake in rat brain synaptosomes
- ChEMBL_142785 Inhibition of reuptake of [3H]-NE (20 nM) by norepinephrine transporter
- ChEMBL_142952 In vitro inhibition of [3H]norepinephrine uptake in rat brain synaptosomes
- ChEMBL_142960 Inhibition of [3H]nisoxetine binding to the norepinephrine transporter in rat midbrain.
- ChEMBL_142965 Selectivity for the norepinephrine transporter using [3H]nisoxetine binding assay
- ChEMBL_143116 Displacement of from norepinephrine transporter of frozen rat caudate membranes
- ChEMBL_143122 Inhibition of 0.5 nM [3H]nisoxetine binding to Norepinephrine transporter
- ChEMBL_143134 Compound was tested for inhibiting reuptake of [3H]- NE by norepinephrine transporter
- ChEMBL_144985 Displacement of [3H]nisoxetine from rat brain norepinephrine transporter
- ChEMBL_144990 Displacement of [3H]NE from Norepinephrine transporter of rat brain
- ChEMBL_177401 Inhibition of uptake of tritiated norepinephrine (NE) into rat brain synaptosomes
- ChEMBL_303198 Inhibition of rat brain Norepinephrine transporter as accumulation of [3H]-NE
- ChEMBL_305586 Inhibition of rat brain Norepinephrine transporter as accumulation of [3H]NE
- ChEMBL_32741 Antagonism of norepinephrine induced contraction of rat isolated thoracic aorta.
- ChEMBL_376176 Inhibition of rat NET-mediated norepinephrine uptake in CHO cells
- ChEMBL_467790 Inhibition of norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_491609 Inhibition of norepinephrine uptake at human NET in human HEK293 cells
- ChEMBL_510054 Inhibition of norepinephrine uptake at human NET expressed in HEK cells
- ChEMBL_510091 Inhibition of norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_523089 Inhibition of norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_535516 Inhibition of norepinephrine uptake at human NET expressed in MDCK cells
- ChEMBL_558433 Inhibition of norepinephrine uptake at human NET transfected in HEK cells
- ChEMBL_589388 Inhibition of norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_654118 Inhibition of norepinephrine reuptake at human NET expressed in MDCK cells
- ChEMBL_976616 Binding affinity to human norepinephrine transporter by ligand displacement assay
- ChEBML_129897 In vitro inhibition of accumulation of (-)-[3H]Norepinephrine (NA) in mouse brain slices
- ChEBML_142631 Inhibition of binding of [3H]nisoxetine to (NET) norepinephrine transporter in rat striatum
- ChEBML_142789 The inhibitory constant(Ki) value for Norepinephrine N-methyl-transferase was calculated
- ChEBML_142958 Inhibition of the NE [3H]norepinephrine uptake by rat brain slices In vitro
- ChEBML_142962 Inhibitory activity against radioligand [3H]nisoxetine binding at the norepinephrine transporter
- ChEBML_143115 Displacement of [3H]-nisoxatine from norepinephrine transporter of rat brain membrane
- ChEBML_143128 Inhibition of [3H]NE binding to norepinephrine transporter of rat brain synaptosomes
- ChEBML_143135 Norepinephrine transporter activity was determined by inhibition of monoamine [3H]-NE reuptake
- ChEBML_143139 Binding affinity towards Norepinephrine transporter using [3H]nisoxitine as radioligand
- ChEBML_144988 Ability to displace [3H]-nisoxatine radioligand for the Norepinephrine transporter in rat brain
- ChEMBL_129897 In vitro inhibition of accumulation of (-)-[3H]Norepinephrine (NA) in mouse brain slices
- ChEMBL_142631 Inhibition of binding of [3H]nisoxetine to (NET) norepinephrine transporter in rat striatum
- ChEMBL_142795 Binding affinity against norepinephrine transporter by using [3H]nisoxetine as a radioligand
- ChEMBL_142799 Inhibition of [3H]norepinephrine uptake in HEK cells expressing human NET
- ChEMBL_142800 Inhibition of [3H]norepinephrine uptake in HEK cells expressing human NET
- ChEMBL_142802 Inhibition of [3H]- NE uptake in HEK cells expressing norepinephrine transporter
- ChEMBL_142955 Inhibition of norepinephrine transporter (NET) determined using [3H]nisoxetine radioligand.
- ChEMBL_142962 Inhibitory activity against radioligand [3H]nisoxetine binding at the norepinephrine transporter
- ChEMBL_142963 Inhibitory concentration binding to Norepinephrine transporter using 0.2 nM paroxetine
- ChEMBL_142970 Displacement of [3H]-nisoxatine from Norepinephrine transporter of rat forebrain membrane
- ChEMBL_143110 Displacement of [3H]nisoxetine from norepinephrine transporter (NET) of rat brain
- ChEMBL_143115 Displacement of [3H]-nisoxatine from norepinephrine transporter of rat brain membrane
- ChEMBL_143124 Inhibition of [3H]NE uptake by rat frontal cortex Norepinephrine transporter
- ChEMBL_143128 Inhibition of [3H]NE binding to norepinephrine transporter of rat brain synaptosomes
- ChEMBL_143135 Norepinephrine transporter activity was determined by inhibition of monoamine [3H]-NE reuptake
- ChEMBL_144967 Inhibition of Norepinephrine (NA) reuptake using cloned human transporter was determined
- ChEMBL_144977 Binding affinity at the norepinephrine transporter in rat striatum by [3H]nisoxetine displacement.
- ChEMBL_144982 Inhibitory concentration binding to Norepinephrine transporter using 0.2 nM paroxetine
- ChEMBL_144988 Ability to displace [3H]-nisoxatine radioligand for the Norepinephrine transporter in rat brain
- ChEMBL_144998 Inhibitory constant against norepinephrine transporter receptor using [3H]radioligand
- ChEMBL_303224 Inhibition of [3H]nisoxetine binding to rat norepinephrine transporter at 10 uM
- ChEMBL_303312 Displacement of [3H]nisoxetine from norepinephrine transporter of rat cerebral cortex
- ChEMBL_303514 Inhibition of [3H]-nisoxetine binding to Norepinephrine transporter from rat cortex
- ChEMBL_303519 Binding affinity for Norepinephrine transporter (NET) expressed in LCK PK1 cells
- ChEMBL_306091 Inhibition of [3H]nisoxetine binding to norepinephrine transporter of rat cerebral cortex
- ChEMBL_306351 Inhibition of [3H]nisoxetine binding to rat cerebral cortex norepinephrine transporter
- ChEMBL_334929 Inhibition of [3H] norepinephrine uptake into human NET expressed in HEK293 cells
- ChEMBL_34043 Antagonism of the norepinephrine induced contraction of rat isolated prostatic vas deferens.
- ChEMBL_348646 Inhibition of potassium-evoked [3H]norepinephrine release from rat neocortex
- ChEMBL_469595 Displacement of [3H]nisoxetine from norepinephrine transporter in rat brain homogenate
- ChEMBL_499923 Inhibition of [3H]norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_500244 Inhibition of norepinephrine uptake at human NET expressed in MDCK-Net6 cells
- ChEMBL_541290 Inhibition of [3H]norepinephrine reuptake at human NET expressed in HEK cells
- ChEMBL_558178 Inhibition of norepinephrine uptake at human NET expressed in MDCK-Net6 cells
- ChEMBL_595700 Inhibition of [3H]norepinephrine reuptake at human NET expressed in HEK293 cells
- ChEMBL_598114 Inhibition of norepinephrine reuptake at human NET expressed in MDCK-Net6 cells
- ChEMBL_610770 Inhibition of [3H]norepinephrine uptake at human NET expressed in HEK293 cells
- ChEMBL_611007 Inhibition of norepinephrine uptake at human NET expressed in MDCK-Net6 cells
- ChEMBL_617684 Inhibition of norepinephrine uptake at human NET expressed in MDCK-Net6 cells
- ChEMBL_634326 Inhibition of human NET-mediated norepinephrine uptake in MDCK-Net6 cells
- ChEBML_142786 Inhibitory activity against Norepinephrine N-methyl-transferase of bovine adrenal glands
- ChEBML_142787 Inhibitory activity against bovine adrenal norepinephrine N-methyl-transferase was determined
- ChEBML_142807 Ability to inhibit [3H]nisoxetine binding to cloned human norepinephrine (NE) transporter
- ChEBML_144987 Inhibition of [3H]-NE reuptake at Norepinephrine transporter in rat parietal/occipital cortex
- ChEBML_144989 Compound was tested for the inhibition of norepinephrine [3H]NE reuptake into rat cortical membranes
- ChEBML_145001 Compound was tested for inhibition of [3H]NE binding to norepinephrine transporter HEK cells
- ChEMBL_140880 Inhibition of [3H]NE reuptake by human norepinephrine transporter expressed in HEK293 cells
- ChEMBL_140881 Binding affinity at the norepinephrine transporter was measured using [125I]RTI-55 as a radioligand
- ChEMBL_140882 Compound was evaluated for its binding affinity towards human NET (norepinephrine) transporter
- ChEMBL_140883 Compound was evaluated for its binding affinity towards human NET(norepinephrine) transporter
- ChEMBL_142628 Concentration causing 50% Inhibition of binding of [3H]- nisoxatine to Norepinephrine transporter (NET).
- ChEMBL_142630 Inhibition of binding of [3H]- nisoxatine to Norepinephrine transporter (NET) of rat cerebral cortex.
- ChEMBL_142639 Inhibition of [3H]NE uptake by Norepinephrine transporter of rat occipital cortex synaptosomes
- ChEMBL_142640 Inhibition of [3H]NE uptake by Norepinephrine transporter of rat occipital cortex synaptosomes
- ChEMBL_142779 Compound was tested for its ability to displace [3H]citalopram from norepinephrine transporter
- ChEMBL_142783 Inhibition of [3H]nisoxetine binding to norepinephrine transporter (NET) of rat cortical homogenates
- ChEMBL_142786 Inhibitory activity against Norepinephrine N-methyl-transferase of bovine adrenal glands
- ChEMBL_142807 Ability to inhibit [3H]nisoxetine binding to cloned human norepinephrine (NE) transporter
- ChEMBL_142942 Affinity at norepinephrine transporter (NET) in rat striatum, using [3H]- nisoxatine as radioligand
- ChEMBL_142943 Binding affinity against Norepinephrine transporter using [3H]nisoxetine in midbrain of rat
- ChEMBL_142945 Binding affinity towards norepinephrine transporter was determined by using [3H]nisoxetine radioligand
- ChEMBL_142961 Inhibitory activity against Norepinephrine transporter using 0.5 nM [3H]-radioligand
- ChEMBL_142969 Displacement of [3H]nisoxetine from norepinephrine transporter (NET) in rat brain membranes
- ChEMBL_143109 Binding affinity for norepinephrine transporter in rat brain using [3H]-nisoxatine as radioligand
- ChEMBL_143112 Binding affinity towards norepinephrine transporter was determined using [3H]nisoxetine radioligand.
- ChEMBL_143140 Compound was evaluated for binding to Norepinephrine Transporter (NET) using [3H]desmethylimipramine as radioligand
- ChEMBL_144983 Ability to inhibit [3H]NE reuptake at norepinephrine transporter from rat brain
- ChEMBL_144986 Binding affinity towards norepinephrine transporter using [3H]nisoxetine as radioligand was determined
- ChEMBL_144987 Inhibition of [3H]-NE reuptake at Norepinephrine transporter in rat parietal/occipital cortex
- ChEMBL_145001 Compound was tested for inhibition of [3H]NE binding to norepinephrine transporter HEK cells
- ChEMBL_1452255 Displacement of [3H]Nisoxetine from human Norepinephrine transporter by liquid scintillation counting
- ChEMBL_1558447 Inhibition of recombinant human norepinephrine transporter assessed as reduction in [3H]-NA reuptake
- ChEMBL_302942 In vitro binding affinity against norepinephrine transporter using [3H]-nisoxetine as radioligand
- ChEMBL_303548 Displacement of [3H]nisoxetine from norepinephrine transporter (NET) of rat cerebral cortex
- ChEMBL_303591 Displacement of [3H]-nisoxetine from norepinephrine transporter of rat cerebral corticex homogenate
- ChEMBL_699309 Inhibition of [3H]norepinephrine reuptake at NET in rat brain synaptosome by scintillation counting
- ChEMBL_741840 Inhibition of human NET in HEK293 cells assessed as inhibition of [3H]norepinephrine uptake
- ChEBML_142968 Ability to displace [3H]- nisoxetin from Norepinephrine transporter in rat cerebral cortical homogenate
- ChEBML_143108 Binding affinity at norepinephrine transporter using [3H]nisoxetine as radioligand from rat brain
- ChEBML_143123 Inhibition of [3H]NE uptake at Norepinephrine transporter in rat parietal/occipital cortex was determined
- ChEBML_143125 Inhibition of norepinephrine transporter by inhibition of [3H]NE uptake into rat nerve endings (synaptosomes)
- ChEMBL_142613 Compound was tested for inhibition of [125I]-RTI-55 binding to norepinephrine transporter HEK cells
- ChEMBL_142614 Inhibition of [125I]- RTI -55 binding at the Norepinephrine transporter sites on HEK-hNET cells
- ChEMBL_142632 The binding affinity at the Norepinephrine transporter reuptake sites determined using competition binding assay
- ChEMBL_142935 Inhibition of [125I]RTI-55 binding to norepinephrine transporter (NET) expressed in HEK cells
- ChEMBL_142947 Binding affinity towards Norepinephrine transporter was determined using NE[3H]Nisoxetine as radioligand
- ChEMBL_143123 Inhibition of [3H]NE uptake at Norepinephrine transporter in rat parietal/occipital cortex was determined
- ChEMBL_144975 Binding affinity towards norepinephrine transporter in rat striatum using [3H]nisoxetine as radioligand
- ChEMBL_145004 Displacement of [125I]RTI-55 from human Norepinephrine transporter expressed in HEK cells
- ChEMBL_1559990 Displacement of [3H]nisoxentine from human recombinant norepinephrine transporter expressed in CHO cells
- ChEMBL_1654664 Inhibition of NET (unknown origin) expressed in HEK293 cells assessed as reduction in norepinephrine reuptake
- ChEMBL_193312 Inhibitory activity against norepinephrine (NE) uptake in rat whole brain synaptosome preparation
- ChEMBL_302666 Inhibitory constant for [3H]NE reuptake at norepinephrine transporter of rat parietal-occipital cortex
- ChEMBL_303505 In vitro displacement of [3H]nisoxetine from human norepinephrine transporter expressed in HEK293 cells
- ChEMBL_303772 In vitro inhibition of [3H]nisoxetine binding to norepinephrine transporter expressed in human kidney cells
- ChEMBL_306359 Displacement of [125I]RTI-55 from human Norepinephrine transporter expressed in HEK293 cells
- ChEMBL_487421 Displacement of [3H]nisoxetine from human norepinephrine transporter expressed in MDCK-Net6 cells
- ChEMBL_62322 Displacement of [125I]RTI-55 from human Norepinephrine transporter expressed in HEK cells
- ChEMBL_699305 Inhibition of [3H]norepinephrine reuptake at human NET expressed in MDCK cells by scintillation counting
- ChEMBL_769841 Inhibition of human NET expressed in MDCK-Net6 cells assessed as inhibition of norepinephrine uptake
- ChEMBL_974162 Displacement of [3H]-norepinephrine from human NET expressed in CHO cells by TopCounting analysis
- ChEBML_142934 Binding affinity to norepinephrine (NE) transporter in membranes of cells selectively expressing the human genes for NET
- ChEBML_142939 Binding affinity to Norepinephrine transporter using [3H]-nisoxatine as radioligand in stably transfected NIH3T3 cells
- ChEBML_143133 Binding affinity towards norepinephrine transporter by displacement of [3H]nisoxetine radioligand from rat brain
- ChEMBL_142624 50% Inhibition against Norepinephrine transporter in rat cerebral cortex by displacing [3H]nisoxetine radioligand
- ChEMBL_142804 The compound was tested in vitro for binding affinity for the norepinephrine transporter (NET) using competitive binding assay.
- ChEMBL_142951 Inhibition of norepinephrine Transporter Affinity against rat whole brain using [3H]nisoxetine radioligand
- ChEMBL_143106 Affinity for the displacement of [3H]paroxetine binding to norepinephrine transporter (NET) in rat frontal cortex membranes
- ChEMBL_143133 Binding affinity towards norepinephrine transporter by displacement of [3H]nisoxetine radioligand from rat brain
- ChEMBL_1442873 Induction of NET-mediated norepinephrine release in rat brain synaptosomes by [3H]NE release assay
- ChEMBL_1442878 Inhibition of NET-mediated norepinephrine release in rat brain synaptosomes by [3H]NE release assay
- ChEMBL_144974 Binding affinity against norepinephrine transporter (NET) by displacement of [3H]nisoxetine in male wistar rats
- ChEMBL_144984 Binding affinity against norepinephrine transporter (NET) by displacement of [3H]nisoxetine in male wistar rats
- ChEMBL_1456969 Inhibition of [3H]-NE uptake in human norepinephrine transporter expressed in HEK293 cells by scintillation counting
- ChEMBL_2068294 Displacement of [3H]nisoxetine from norepinephrine transporter (unknown origin) by liquid scintillation counting method
- ChEMBL_302728 Inhibitory constant against reuptake of [3H]NE at norepinephrine transporter of rat parietal-occipital cortex
- ChEMBL_574171 Antagonist activity at rat alpha1A adrenoceptor assessed as inhibition if norepinephrine-induced contraction of vas deference
- ChEMBL_583225 Inhibition of [3H]norepinephrine uptake at human NET expressed in MDCK-Net6 cells by scintillation counting
- ChEMBL_726960 Inhibition of [3H]norepinephrine reuptake at human recombinant NET expressed in HEK293 cells by scintillation counting
- ChEMBL_792745 Inhibition of [3H]norepinephrine reuptake at human NET cloned in rat brain synaptosome by scintillation counting
- ChEBML_142788 Tested for inhibitory activity against bovine adrenal norepinephrine N-methyl-transferase using phenylethanolamine as substrate
- ChEBML_142806 Equilibrium dissociation constant (KD) for Competitive binding between [3H]- nisoxatine and the compound at human Norepinephrine transporter
- ChEBML_142946 Binding affinity was evaluated by measuring inhibiting the binding of [3H]nisoxetine to Norepinephrine transporter in rat brain tissue
- ChEMBL_142645 Tested for the binding affinity towards Norepinephrine transporter in rat cerebral cortex by displacing [3H]nisoxetine radioligand
- ChEMBL_142784 Binding affinity against norepinephrine cloned human transporter using 40-80 pM [125I]RTI
- ChEMBL_142794 Compound was evaluated for inhibition of [3H]NE uptake in HEK-hNET cells expressing Human norepinephrine transporter
- ChEMBL_142940 In vitro binding affinity against monoamine transporter NET (norepinephrine transporter) in LLC-PK1 cell membranes.
- ChEMBL_142944 Binding affinity at the Norepinephrine transporter in rat frontal cortex by inhibition of 0.5 nM [3H]nisoxetine binding
- ChEMBL_142946 Binding affinity was evaluated by measuring inhibiting the binding of [3H]nisoxetine to Norepinephrine transporter in rat brain tissue
- ChEMBL_143121 In vitro binding affinity towards Norepinephrine transporter rat cerebral cortical homogenates by [3H]nisoxetine displacement.
- ChEMBL_1505018 Inhibition of human NET expressed in CHOK1 cells incubated for 45 mins by [3H]-norepinephrine uptake assay
- ChEMBL_197580 Binding affinity against human cloned norepinephrine transporter using 40-80 pM [125I]RTI.
- ChEMBL_33178 In vitro ability to inhibit norepinephrine binding to alpha-2 adrenergic receptor of guinea pig vas deferens
- ChEBML_1711465 Displacement of [3H]nisoxetine from recombinant human norepinephrine transporter after 120 mins by scintillation counting analysis
- ChEMBL_142619 In vitro binding affinity in LLC-PK1 cells by Norepinephrine transporter binding assay by using [125I]-IPT as a radioligand
- ChEMBL_142636 Inhibition of high affinity uptake of [3H]NE by norepinephrine transporter in nerve endings obtained from rat brain.
- ChEMBL_142637 Binding affinity for Norepinephrine transporter is assessed from the ability to displace [3H]nisoxetine from rat frontal cortex
- ChEMBL_142954 In vitro inhibitory activity against radioligand [3H]-nisoxatine binding to norepinephrine transporter (NET) in rat cortical tissue
- ChEMBL_1456596 Inhibition of [3H]norepinephrine reuptake at human NET expressed in CHO cells after 45 mins by scintillation counting
- ChEMBL_1745411 Displacement of [3H]nisoxetine from recombinant human norepinephrine transporter after 120 min by scintillation counting method
- ChEMBL_1864054 Displacement of [3H]nisoxetine from recombinant human norepinephrine transporter after 120 mins by scintillation counting analysis
- ChEMBL_1929929 Inhibition of [3H]-5-norepinephrine reuptake in human NET expressed in HEK293 cells by liquid scintillation counting method
- ChEMBL_641577 Inhibition of [3H]norepinephrine reuptake at human NET expressed in HEK293 cells after 90 mins by scintillation counting
- ChEMBL_806517 Displacement of [3H]nisoxetine from human recombinant norepinephrine transporter expressed in CHO cells after 120 mins
- ChEMBL_142936 Compound was tested for its affinity by the inhibition of [125I]RTI-55 binding at norepinephrine transporter (NET) transfected in HEK cells
- ChEMBL_142971 Ability to inhibit high affinity uptake of norepinephrine transporter into the nerve endings of rat synaptosomes using [3H]NE as a radioligand
- ChEMBL_142972 Ability to inhibit high affinity uptake of norepinephrine transporter into the nerve endings of rat synaptosomes using [3H]NE radioligand
- ChEMBL_144972 In vitro competitive binding versus [3H]- nisoxatine in murine kidney cells transfected with cDNA for human norepinephrine transporter (NET)
- ChEMBL_144973 In vitro competitive binding versus [3H]- nisoxatine in murine kidney cells transfected with cDNA for human norepinephrine transporter (NET)
- ChEMBL_1455467 Inhibition of norepinephrine reuptake at human NET expressed in HEK293 cells after 15 mins by fluorescence neurotransmitter transporter assay
- ChEMBL_1657815 Inhibition of [3H]-5-norepinephrine reuptake in human NET expressed in HEK293 cells by microbeta liquid scintillation counting method
- ChEMBL_303717 Inhibition of high affinity uptake by the norepinephrine transporter from rat synaptosomal nerve endings by using [3H]NE as radioligand
- ChEMBL_33177 Alpha-2-adrenolytic activity was assessed in vitro from the ability to inhibit norepinephrine binding to guinea pig vas deferens
- ChEBML_143120 In vitro binding affinity of compound for Norepinephrine (NE) transporter with [3H]- nisoxatine as radioligand in corpus striatum tissue from rat forebrain
- ChEMBL_142607 Ability to displace [125I]- RTI-55 binding at the Norepinephrine transporter site on HEK cells expressing cDNA for the human transporter (hNET)
- ChEMBL_142635 Ability to inhibit high affinity reuptake of [3H]-NE (Norepinephrine transporter) into nerve ending synaptosomes prepared from brain regions
- ChEMBL_142793 Compound was evaluated for binding affinity using [125I]RTI-55 as a radioligand in HEK-hNET cells expressing human norepinephrine transporter
- ChEMBL_143105 Ability to inhibit high affinity uptake of [3H]NE at Norepinephrine transporter (NET) using rat brain parietal/occipital cortex
- ChEMBL_144969 In vitro binding affinity against human norepinephrine transporter in human embryonic kidney cell line by using [3H]-nisoxatine radioligand
- ChEMBL_1513492 Antagonist activity at human alpha1B adrenoceptor assessed as inhibition of norepinephrine-induced increase of intracellular calcium level by cell based assay
- ChEMBL_1651928 Displacement of [3H]nisoxetine from human recombinant norepinephrine transporter expressed in CHO cells after 120 mins by scintillation counting
- ChEMBL_490890 Displacement of [125I]PIC from human imidazoline receptor 1 in human platelets analyzed under norepinephrine mask of alpha 2AR
- ChEMBL_493240 Displacement of Levo[ring-2,5,6-3H]norepinephrine from human cloned NET expressed in HEK293 cells by microplate scintillation counter
- ChEMBL_493243 Displacement of Levo[ring-2,5,6-3H]norepinephrine from rat synaptosomal NET expressed in HEK293 cells by microplate scintillation counter
- Functional Uptake Assay (rNET) Quantification of norepinephrine uptake was performed using synaptosomes isolated in a 0.32 M sucrose buffer from a male Wistar rat hypothalamus. The uptake of radiolabelled norepinephrine by synaptosomes (100 ug of proteins/point) was allowed by incubating them for 20 minutes at 37° C. in presence of test compounds and [3H]-norepinephrine (0.1 uCi/point). The experiment was performed in a deep well. Synaptosomes and [3H]-norepinephrine were prepared in a Krebs buffer pH 7.4 containing 25 mM NaHCO3, 11 mM glucose and 50 uM ascorbic acid. This incubation buffer was oxygenated for 5 minutes before incubation. Basal control was incubated for 20 minutes at 4° C. in order to avoid any uptake. Following this incubation, the uptake was stopped by filtration through a unifilter 96-wells GFB Packard plate washed with Krebs buffer containing 25 mM NaHCO3 in order to eliminate the free [3H]-norepinephrine.
- ChEBML_143114 Compound has been evaluated for its affinity towards Norepinephrine transporter by displacing the radio isotope [3H]nisoxetine from rat forebrain
- ChEMBL_1356559 Inhibition of [3H]norepinephrine uptake at NET expressed in rat hypothalamic homogenate containing synaptosomes after 5 mins by scintillation counting analysis
- ChEMBL_144968 In vitro binding affinity against human norepinephrine transporter in human embryonic kidney cell line using [125I]RTI-55 as radioligand
- ChEMBL_144970 In vitro binding affinity against human norepinephrine transporter in human embryonic kidney cell line by using [125I]-RTI-55 radioligand
- ChEMBL_1803914 Inhibition of [3H]norepinephrine uptake at human NET expressed in HEK293 cells after 15 to 20 mins by microbeta scintillation counting method
- ChEMBL_687286 Displacement of [3H]nisoxetine from norepinephrine transporter in Sprague-Dawley rat frontal cortex after 1 hr by liquid scintillation counting
- ChEMBL_1617625 Antagonist activity at alpha1A adrenoceptor in Sprague-Dawley rat urethra assessed as inhibition of norepinephrine-induced smooth muscle contraction after 20 mins
- ChEMBL_1617626 Antagonist activity at alpha1B adrenoceptor in Sprague-Dawley rat aorta assessed as inhibition of norepinephrine-induced smooth muscle contraction after 20 mins
- ChEMBL_1633616 Displacement of [3H]nisoxetine from human recombinant norepinephrine transporter expressed in CHO cells measured after 120 mins by scintillation counting method
- Functional Uptake Assay (hNET) Inhibition of human norepinephrine reuptake transporter was assayed using the recombinant human norepinephrine transporter expressed in either HEK293 or MDCK cells using a published method (Galli A et al., J. Exp. Biol. 198: 2197-2212, 1995). The cells were plated before the assay. Test compound and/or vehicle was preincubated with cells in modified HEPES buffer pH 7.1 or pH 7.4 for 20 minutes at 18 to 25° C. Following the preincubation, 25 nM [3H]norepinephrine was added for an additional timed incubation period (10 to 20 minutes). After the cells were washed to remove [3H]norepinephrine not internalized, the cells were lysed, and the amount of tritium in the cell lysate was measured using a liquid scintillation counter to determine [3H]norepinephrine uptake. Non-specific binding of tritium was measured in a control reaction containing 10 uM imipramine (or 10 uM nisoxetine), and was subtracted from the counts for assays to correct for non-specific binding of tritium.
- ChEBML_144978 Evaluated for ability to inhibit high affinity uptake of [3H]-NE using rat nerve endings obtained from brain regions enriched in Norepinephrine transporter
- ChEMBL_144978 Evaluated for ability to inhibit high affinity uptake of [3H]-NE using rat nerve endings obtained from brain regions enriched in Norepinephrine transporter
- ChEMBL_1586596 Inhibition of human NET expressed in CHO cells assessed as [3H]-Norepinephrine reuptake incubated for 45 mins measured after 30 mins by topcount method
- ChEMBL_2062317 Inhibition of human NET expressed in CHO-K1 cells assessed as inhibition of [3H]-norepinephrine reuptake measured after 45 mins by Microscintillation counting analysis
- ChEMBL_753884 Antagonist activity at human adrenergic alpha1A receptor expressed in HEK293 cells assessed as inhibition of norepinephrine-induced [3H]inositol phosphate hydrolysis by scintillation counting
- ChEMBL_144979 Evaluated for its ability to inhibit high affinity uptake of [3H]NE using rat nerve endings obtained from brain regions enriched in norepinephrine transporter (NET)
- ChEMBL_1661733 Inhibition of recombinant human NET expressed in HEK293 cell membranes assessed as reduction in [3H]-norepinephrine uptake incubated for 22 mins by micro beta scintillation counting analysis
- ChEMBL_1777922 Inhibition of voltage-dependent L-type calcium channel in Wistar rat 3rd-order mesenteric artery assessed as reduction in norepinephrine-induced vessel contraction by myographic method
- ChEMBL_2110695 Agonist activity at beta2 adrenoceptor (unknown origin) expressed in sf9 cells assessed as reversal of norepinephrine inhibition of [3H]DHAP binding to beta2 adrenoceptor by radioligand binding assay
- ChEMBL_753885 Antagonist activity against human cloned adrenergic Alpha-1B receptor expressed in HEK293 cells assessed as inhibition of norepinephrine-induced [3H]inositol phosphate hydrolysis by scintillation counting
- ChEMBL_753973 Antagonist activity against human cloned adrenergic Alpha-1D receptor expressed in HEK293 cells assessed as inhibition of norepinephrine-induced [3H]inositol phosphate hydrolysis by scintillation counting
- ChEMBL_1824642 Inhibition of human N-terminal His6 tagged PNMT using norepinephrine as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH enzyme coupled assay
- Norepinephrine, Transporter NET (h) Assay Type: BindingSpecies: HumanOrigin: Recombinant/CHO cellsLigand: [3H]-NisoxetineLigand [M]: 1.00E-09Kd (Binding Affinity): 3.00E-09Bmax: 10 pmol/mg proteinMethod: RadioactivityMeasurement: DPM
- ChEMBL_1742585 Inhibition of c-terminal hexa-His tagged human MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay
- ChEMBL_1742588 Inhibition of c-terminal hexa-His tagged rat MB-COMT expressed in HEK293 cell membrane homogenate using norepinephrine as substrate after 1 hr in presence of SAM by MTase glo methyltransferase assay
- Radioligand Binding Assay (Ki) and Norepinephrine Uptake Assay (IC50) Compounds were evaluated the inhibition of [3H] nisoxetine binding to MDCK-Net6 cells, stably transfected with the human norepinephrine transporter (hNET). Data from wells containing 1 uM desipramine were used to define non-specific hNET binding. Total radioligand bound is defined by addition of binding buffer alone in the presence of [3H]nisoxetine (Perkin-Elmer). The radioligand binding reaction was initiated by addition of [3H]nisoxetine, and incubated for 2 h at 37 deg C. The KD value estimated for [3H]nisoxetine was 10 nM using intact whole cells. The inhibition constant (Ki) was calculated by the Cheng and Prusoff equation. IC50 Values were obtained from inhibition of norepinephrine uptake in MDCK-Net6 cells, stably transfected with the human NET.
- Binding Assay NE transporter binding assay for evaluating binding of the compound to the norepinephrine transporter was carried out using human recombinant norepinephrine transporter membrane (PerkinElmer Life and Analytical Sciences, USA) expressed in MDCK cells and radioisotope [3H]Nisoxetine (PerkinElmer).That is, the test drug, 6 nM [3H]Nisoxetine, norepinephrine transporter membrane (11 ug/well), 120 mM NaCl and 50 mM Tris-HCl buffer (pH 7.4) containing 5 mM KCl were added to obtain a reaction mixture with a final volume of 0.25 ml. After incubation for 60 minutes at 4° C., the mixture was quickly passed through a Filtermat A glass fiber filter pre-soaked with 0.5% (w/v) PEI (polyethyleneimine) using Inotech Harvester (Inotech) to terminate the reaction. After washing with cold washing buffer (50 mM Tris-HCl, pH 7.4, 0.9% NaCl) solution, the filter was covered with MeltiLex and sealed in a sample bag. After drying in an oven, radioactivity was counted using MicroBeta Plus (Wallac).
- Radioligand Binding Assay (Ki) Compounds were evaluated the inhibition of [3H] nisoxetine binding to MDCK-Net6 cells, stably transfected with the human norepinephrine transporter (hNET). Data from wells containing 1 uM desipramine were used to define non-specific hNET binding. Total radioligand bound is defined by addition of binding buffer alone in the presence of [3H]nisoxetine (Perkin-Elmer). The radioligand binding reaction was initiated by addition of [3H]nisoxetine, and incubated for 2 h at 37 deg C. The KD value estimated for [3H]nisoxetine was 10 nM using intact whole cells. The inhibition constant (Ki) was calculated by the Cheng and Prusoff equation.
- Uptake Assay Protocol NET: This protocol was designed to measure inhibition of uptake by the human norepinephrine transporter. The reagents were human NET (HEK293F) cells, desipramine (Sigma), nomifensine, neurotransmitter transporter uptake assay kit (Molecular Devices), freestyle 293 expression medium (Invitrogen), 10× Hank's Balanced Salt Solution (HBSS; Invitrogen), 1 M HEPES (Mediatech), Biocoat poly-D-lysine 96-well, black, clear plates (Becton, Dickinson), and 500 μL polypropylene U-bottom 96-well plates (Fisher). The Assay Buffer (AB) was 1×HBSS and 0.02 M HEPES.The HEK293F cells were transfected with the human norepinephrine transporter and frozen in 1 mL aliquots at about 1E+07 cells/mL. On the day of the experiment, the cells were removed from −80° C. or liquid nitrogen and thawed in a room temperature water bath. The cells were dilute to about 1-2E+06 with Freestyle medium. A 1 mL sample (1:2 dilution) was prepared, and the cells were counted. The cells were spun at 1100 rpm for 5 minutes, and the medium was aspirated off. The cells were resuspend in medium at 1.5E+06 cells/mL for about 60,000 cells per well. 40 μL of cells were dispensed per well in the Biocoat plates. The plates were spun at 1100 rpm for 1 minute to improve homogeneity of the cell layer and were incubated at 37° C. for a minimum of 3 hours.
- Radioligand Binding Assay The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays.
- Binding Assay NET: Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding 1 μM. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
- Radioligand Binding Assay The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275 (6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
- Binding Assay Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding 10 μM desipramine. The binding of the test compound was measured in five different concentrations. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
- Binding Assay Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding desipramine 10 μM. The binding of the test compound was measured at five different concentrations. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 h and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
- Radioligand Binding Assay (Ki) and Inhibition of Substrate Uptake (EC50/IC50) Binding affinity of each compound was measured by assessing the potency of inhibition of binding of radiolabeled RTI-55. Membranes were preincubated with compound before the addition of [125I]RTI-55. The reaction was terminated by filtration through Whatman GF/C filters using a 96-well Tomtech cell harvester (Tomtech, Orange, CT). Scintillation fluid was added to each filter spot and radioactivity remaining on the filter was determined using a Wallace beta-plate reader. IC50 values were converted to Ki values using the Cheng-Prusoff equation. Specific binding was defined as the difference in binding observed in the presence and absence of 5 uM mazindol (HEK-hDAT and -NET) or 5 uM imipramine (HEK-hSERT). EC50/IC50 values were obtained from inhibition of the reuptake of [3H] dopamine for DAT, [3H] serotonin for SERT, or [3H] norepinephrine for NET.
- In Vitro Pharmacology Assay The monoamine transporters inhibitory activities of selected cycloalkylmethylamines of Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nM to 1 μM.
- Radioligand Binding Assay The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
- Norepinephrine Transporter Binding Assay Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
- Binding Assay Norepinephrine Transporter Binding Assay. Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000×g for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.). Each compound was tested with concentrations ranging from 0.01 nM to 100 mM for competition against binding of [3H]Nisoxetine, in at least three independent experiments, each performed in triplicate.
- Norepinephrine Transporter Binding Assay 1. Each tube receives the following components: 25 ul drug or vehicle 25 ul [3H]-Nisoxetine 200 ul tissue suspension. 2. Initiate binding reaction with the addition of tissue, and incubate at room temperature for 1 hour. 3. Terminate binding reaction by rapid filtration of tube contents onto 0.1% PEI treated GF/C filters (TopCount). 4. Rinse the assay tubes once with ice cold 50 mM NaCl, then rapidly rinse the filters with 6×1 ml/tube of the same wash buffer. 5. Radioactivity trapped onto the filters is assessed using liquid scintillation spectrophotometer after soaking the filters for at least 1 hour in scintillation cocktail. Materials and Reagents 1. The receptor source is human recombinant/CHO. 2. [3H]-Nisoxetine, diluted to a concentration of 10 nM in assay buffer, is used as the radioligand. Thus, the final ligand concentration is 1 nM. 3. Non specific binding is defined as that remaining in the presence of 1×10−6M desipramine (MW=302.8) (Make fresh: in bag with dessicating rocks 1, dissolves in water 1E-3). 4. The reference compound for the assay is desipramine. Desimpramine is run at following final concentrations: 1×10−10, 2×10−10, 5×10−10, 1×10−9, 2×10−9, 5×10−9, 1×10−8, 2×10−8, 5×10−8, 1×10−7, 2×10−7, 5×10−7M 5. The positive control is any of the above run at the final concentrations of: 1×10−9, 5×10−9, 2×10−8 M. 6. The Kd for the receptor is 3 nM. Buffers MW (g/mole) g/1 L Incubation Buffer: 50 mM Tris, pH 7.4 121 6.06 5 mM KCl 74.6 0.38 120 mM NaCl 58.4 7.02 Wash Buffer: 50 mM NaCl 58.4 3.0