BDBM50342818 (3S,11BS)-TETRABENAZINE CHEMBL519344
BDBM50017701 CHEMBL117785 3-isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one Tetrabenazine (TBZ) TETRABENAZINE 3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-pyrido[2,1-a]isoquinolin-2-one
- Saari, WS; Halczenko, W; Huff, JR; Guare, JP; Hunt, CA; Randall, WC; Lotti, VJ; Yarbrough, GG Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. J Med Chem 27: 1182-5 (1984)
- Yao, Z; Wei, X; Wu, X; Katz, JL; Kopajtic, T; Greig, NH; Sun, H Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors. Eur J Med Chem 46: 1841-8 (2011)
- Ugolev, Y; Segal, T; Yaffe, D; Gros, Y; Schuldiner, S Identification of conformationally sensitive residues essential for inhibition of vesicular monoamine transport by the noncompetitive inhibitor tetrabenazine. J Biol Chem 288: 32160-71 (2013)
- 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)
- [3H]TBZOH Binding Assay Liposomes (1-2 ul) were added to 200 ul of reaction buffer containing 150 mM NaCl, 15 mM Tris-HCl, pH 7.5, and increasing concentrations of [3H]TBZOH (American Radiolabeled Chemicals, St. Louis, MO; 6 Ci/mmol, and Vitrax Radiochemicals, 20 Ci/mmol) at room temperature. The reaction was stopped after 20 min by dilution in ice-cold buffer with 125 uM tetrabenazine and was filtered through 0.22-um GSWP filters (Millipore) presoaked with 125 uM tetrabenazine. Nonspecific binding measured in the presence of 125 uM tetrabenazine was subtracted from the total binding levels.
- [3H]Dihydrotetrabenazine ([3H]DTBZ) Binding Assay Synaptic vesicles were prepared from rat brain using a modification of a previously described procedure (Teng et al., 1998). Briefly, fresh whole brain (excluding cerebellum) was homogenized using a Teflon pestle (clearance 0.003 inches) with 7 vertical strokes at 800 rpm in 20 vol of ice-cold 0.32 M sucrose and centrifuged at 1000 g for 12 min at 4 C. The resulting supernatant (S1) was then centrifuged at 22,000 g for 10 min at 4 C. The synaptosomal pellets (P2) were homogenized in 18 mL of ice-cold Milli-Q water and exposed for 5 min for lysing synaptosomes. Osmolarity was restored by addition of 2 mL of 25 mM HEPES with 100 mM dipotassium tartrate (pH 7.5). Samples were centrifuged at 20,000 g for 20 min at 4 C. to remove lysed synaptosomal membranes. MgSO4 (1 mM) was added to the supernatant (S3), and was centrifuged at 100,000 g for 45 min at 4 C. The final vesicular pellets (P4) were resuspended in ice-cold assay buffer (see below) providing 15 ug protein/100 uL, determined by the method of Bradford (1976) using bovine serum albumin as a the standard. Aliquot parts (100 uL) of suspension of vesicle membrane protein were incubated in assay buffer (25 mM HEPES, 100 mM dipotassium tartrate, 5 mM MgSO4, 0.1 mM EDTA and 0.05 mM EGTA, pH 7.5, at 25 C.) in the presence of 3 nM [3H]DTBZ and at least 7 concentrations (1 nM-1 mM) of compound for 1 hr at room temperature. Nonspecific binding was determined in the presence of 20 uM tetrabenazine, a standard compound. Assays were performed in duplicate using a 96-well plate format. Reactions were terminated by filtration of samples on a Unifilter-96 GF/B filter plates (presoaked in 0.5% polyethylenimine), using a FilterMate harvester (Packard BioScience Co., Meriden, Conn.). After washing 5 times with 350 uL of the ice-cold wash buffer (25 mM HEPES, 100 mM dipotassium tartrate, 5 mM MgSO4 and 10 mM NaCl, pH 7.5), filter plates were dried, sealed and each well filled with 40 uL Packard's MicroScint 20 cocktail. Bound [3H]DTBZ was measured using a Packard TopCount NXT scintillation counter with a Packard Windows NT based operating system.