Isoptpo Hyoscine SCOPOLAMINE BDBM50368127
Scopolamine BDBM50452855 Isoptpo Hyoscine
SCOPOLAMINE METHYL NITRATE SMR000058604 cid_657297 BDBM37635 MLS000028382
BDBM50015725 CHEMBL21823 9-Butyl-7-(3-hydroxy-2-phenyl-propionyloxy)-9-methyl-3-oxa-9-azonia-tricyclo[3.3.1.0*2,4*]nonane; bromide(N-butyl scopolamine bromide) 9-Butyl-7-(3-hydroxy-2-phenyl-propionyloxy)-9-methyl-3-oxa-9-azonia-tricyclo[3.3.1.0*2,4*]nonane; bromide(scopolamine butyl bromide)
BDBM50015727 7-(3-Hydroxy-2-phenyl-propionyloxy)-9,9-dimethyl-3-oxa-9-azonia-tricyclo[3.3.1.0*2,4*]nonane; bromide(scopolamine methyl bromide) CHEMBL293927
3-Hydroxy-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.0*2,4*]non-7-yl ester METHSCOPOLAMINE 7-(3-Hydroxy-2-phenyl-propionyloxy)-9,9-dimethyl-3-oxa-9-azonia-tricyclo[3.3.1.0*2,4*]nonane N-METHYLSCOPOLAMINE BDBM50241132 Methyl scopolamine CHEMBL376897
CHEMBL13030 Benzotropine3-Hydroxy-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.0*2,4*]non-7-yl ester 9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl 3-hydroxy-2-phenylpropanoate BDBM50015720 3-hydroxy-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.0*2,4*]non-7-yl ester ChEMBL_11434 SCOPOLAMINE (hyoscine)3-Hydroxy-2-phenyl-propionic acid 9-methyl-3-oxa-9-aza-tricyclo[3.3.1.0*2,4*]non-7-yl ester
- Kulshreshtha, A; Piplani, P Ameliorative effects of amide derivatives of 1,3,4-thiadiazoles on scopolamine induced cognitive dysfunction. Eur J Med Chem 122: 557-573 (2016)
- Fang, L; Appenroth, D; Decker, M; Kiehntopf, M; Lupp, A; Peng, S; Fleck, C; Zhang, Y; Lehmann, J NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity. J Med Chem 51: 7666-9 (2008)
- Kim, HJ; Jang, BK; Park, JH; Choi, JW; Park, SJ; Byeon, SR; Pae, AN; Lee, YS; Cheong, E; Park, KD A novel chalcone derivative as Nrf2 activator attenuates learning and memory impairment in a scopolamine-induced mouse model. Eur J Med Chem 185: (2020)
- Tao, L; Xie, J; Wang, Y; Wang, S; Wu, S; Wang, Q; Ding, H Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H2O2-induced cytotoxicity in PC12 cells. Bioorg Med Chem Lett 24: 5385-9 (2015)
- Suzuki, F; Shimada, J; Shiozaki, S; Ichikawa, S; Ishii, A; Nakamura, J; Nonaka, H; Kobayashi, H; Fuse, E Adenosine A1 antagonists. 3. Structure-activity relationships on amelioration against scopolamine- or N6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance. J Med Chem 36: 2508-18 (1993)
- Chaudhaery, SS; Roy, KK; Shakya, N; Saxena, G; Sammi, SR; Nazir, A; Nath, C; Saxena, AK Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology. J Med Chem 53: 6490-505 (2010)
- ChEMBL_139581 In vitro for binding affinity for muscarinic acetylcholine receptors in homogenized rat brain in the presence of [3H]scopolamine.
- ChEBML_139082 Inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M1 of transfected A9L cells.
- ChEBML_139254 Inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M4 of NG108-15 cells.
- ChEMBL_139082 Inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M1 of transfected A9L cells.
- ChEMBL_139254 Inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M4 of NG108-15 cells.
- ChEMBL_139918 Inhibition of [3H]- N-methyl-scopolamine ([3H]NMS) dissociation from porcine cardiac M2-receptors
- ChEMBL_140116 Compound was tested for inhibiting [3H]N-Methyl-scopolamine Binding to Muscarinic receptor (M2) in Rat Heart
- ChEMBL_140117 Compound was tested for inhibiting [3H]N-Methyl-scopolamine Binding to Muscarinic receptor (M2) in Rat Heart
- ChEMBL_1522863 Displacement of [3H]N-methyl scopolamine from human cloned muscarinic M3 receptor by dilution method
- ChEMBL_429186 Displacement of [3H]N-methyl-scopolamine from human muscarinic M2 receptor expressed in CHOK1 cells
- ChEMBL_429188 Displacement of [3H]N-methyl-scopolamine from human muscarinic M3 receptor expressed in CHOK1 cells
- ChEMBL_138163 Inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M2 of rat heart tissue membranes.
- ChEMBL_138252 Compound was tested for inhibiting [3H]N-Methyl-scopolamine Binding to Muscarinic receptor (M3) in Rat Submaxillary Gland
- ChEMBL_140052 Inhibitory activity against [3H]N-methyl-scopolamine binding to Muscarinic acetylcholine receptor M2 in rat cerebellum
- ChEMBL_429169 Displacement of [3H]N-methyl-scopolamine from human muscarinic M2 receptor expressed in CHO K1 cells
- ChEMBL_429171 Displacement of [3H]N-methyl-scopolamine from human muscarinic M3 receptor expressed in CHO K1 cells
- ChEMBL_441416 Displacement of 1-[N-methyl- 3H]scopolamine from human muscarinic M1 receptor expressed in Sf9 cells
- ChEMBL_441417 Displacement of 1-[N-methyl- 3H]scopolamine from human muscarinic M2 receptor expressed in Sf9 cells
- ChEMBL_441418 Displacement of 1-[N-methyl- 3H]scopolamine from human muscarinic M3 receptor expressed in Sf9 cells
- ChEMBL_452481 Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic M1 receptor expressed in CHO cells
- ChEMBL_468829 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M1 receptor expressed in CHO cells
- ChEMBL_468830 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M2 receptor expressed in CHO cells
- ChEMBL_468831 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M3 receptor expressed in CHO cells
- ChEMBL_468832 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M4 receptor expressed in CHO cells
- ChEMBL_468833 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M5 receptor expressed in CHO cells
- ChEMBL_815845 Displacement of [3H]-N-methyl scopolamine from muscarinic acetylcholine M1 receptor expressed in CHO cell membrane
- ChEMBL_815846 Displacement of [3H]-N-methyl scopolamine from muscarinic acetylcholine M2 receptor expressed in CHO cell membrane
- ChEMBL_815847 Displacement of [3H]-N-methyl scopolamine from muscarinic acetylcholine M3 receptor expressed in CHO cell membrane
- ChEBML_139909 Allosteric inhibition of [3H]NMS (N-methyl-scopolamine) dissociation from porcine cardiac Muscarinic acetylcholine receptor M2
- ChEMBL_138967 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to Muscarinic acetylcholine receptor M3 of transfected A9L cells.
- ChEMBL_138969 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M3 of transfected A9L cells.
- ChEMBL_139083 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M1 of transfected A9L cells.
- ChEMBL_139084 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M1r of transfected A9L cells.
- ChEMBL_139580 Tested in vitro for binding affinity against Muscarinic acetylcholine receptor from rat brain using [3H]- Scopolamine as radioligand
- ChEMBL_479202 Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic receptor M1 expressed in CHO cell membrane
- ChEBML_138164 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M2 of rat heart tissue membranes
- ChEMBL_138164 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M2 of rat heart tissue membranes
- ChEMBL_138165 The compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to muscarinic acetylcholine receptor M2 of rat heart tissue membranes.
- ChEMBL_138637 Inhibit the binding of [N-mnethyl-3H]-scopolamine [3H]-NMS) to Muscarinic acetylcholine receptor of human IRM-30 neuroblastoma cells
- ChEMBL_138963 Compound was tested for the inhibition of binding of [3H]N-Methyl-scopolamine to mmuscarinic acetylcholine receptor M3 of transfected rat A9L cells
- ChEMBL_139265 Compound was tested for inhibiting [3H]N-Methyl-scopolamine Binding to Muscarinic acetylcholine receptor M4 in NG 108-15 Cell
- ChEMBL_726947 Displacement of [3H]-N-methyl-scopolamine from human muscarinic M3 receptor after 6 hrs by cell based assay
- ChEMBL_745281 Displacement of [3H]N-methyl Scopolamine from human muscarinic M3 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_750514 Displacement of [3H]N-methyl Scopolamine from human muscarinic M1 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_750515 Displacement of [3H]N-methyl Scopolamine from human muscarinic M2 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_750516 Displacement of [3H]N-methyl Scopolamine from human muscarinic M3 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_140053 Inhibitory activity against [3H]N-methyl-scopolamine in rat Muscarinic acetylcholine receptor M2 cerebellum in the presence GPP(NH)P
- ChEMBL_2150070 Displacement of [3H]-N-methyl Scopolamine Chloride from human M3 receptor membranes incubated for 2 hrs by scintillation counting analysis
- ChEMBL_2150084 Displacement of [3H]-N-methyl Scopolamine Chloride from human M2 receptor membranes incubated for 2 hrs by scintillation counting analysis
- ChEMBL_510510 Displacement of [3H]N-methyl Scopolamine from human muscarinic acetylcholine M1 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_510512 Displacement of [3H]N-methyl Scopolamine from human muscarinic acetylcholine M3 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_539023 Displacement of [3H]N-methyl Scopolamine from human cloned muscarinic M3 receptor expressed in CHO cells by scintillation proximity assay
- ChEMBL_584294 Displacement of [3H]N-methyl Scopolamine from human muscarinic M1 receptor expressed in CHO Flp-In cells by liquid scintillation assay
- ChEMBL_630094 Displacement of [3H]N-methyl Scopolamine from human muscarinic M1 receptor expressed in CHO Flp-In cells by liquid scintillation counting
- ChEMBL_510511 Displacement of [3H]N-methyl Scopolamine from human muscarinic acetylcholine M2 receptor expressed in CHO cells coexpressed with Gqi5 by scintillation proximity assay
- ChEMBL_562971 Displacement of [3H]N-methyl scopolamine from human cloned muscarinic M1 receptor expressed in CHO cells coexpressing Gqi5 by scintillation proximity assay
- ChEMBL_562972 Displacement of [3H]N-methyl scopolamine from human cloned muscarinic M2 receptor expressed in CHO cells coexpressing Gqi5 by scintillation proximity assay
- ChEMBL_562973 Displacement of [3H]N-methyl scopolamine from human cloned muscarinic M3 receptor expressed in CHO cells coexpressing Gqi5 by scintillation proximity assay
- ChEBML_140184 Compound was evaluated for its affinity towards Muscarinic acetylcholine receptor M2, using [3H]- N-methyl-scopolamine, a radioligand displacement assay in rat heart membranes
- ChEMBL_138184 Compound was evaluated for its ability to displace [3H]- N-methyl-scopolamine ([3H]NMS) binding to cloned CHO cell lines expressing Muscarinic acetylcholine receptor M2
- ChEMBL_138321 In vitro binding affinity towards Muscarinic acetylcholine receptor M3 was determined by measuring its ability to displace [3H]-N-methyl- Scopolamine from guinea pig ileum
- ChEMBL_139261 Compound was evaluated for its ability to displace [3H]- N-methyl-scopolamine ([3H]-NMS) binding to cloned CHO cell lines expressing Muscarinic acetylcholine receptor M4
- ChEMBL_139520 Compound was evaluated for its ability to displace [3H]- N-methyl-scopolamine ([3H]NMS) binding to cloned CHO cell lines expressing Muscarinic acetylcholine receptor M5
- ChEMBL_982012 Displacement of N-methyl [3H]-scopolamine from recombinant human muscarinic acetylcholine receptor M2 expressed in CHO cells after 2 hrs by liquid scintillation counting
- ChEMBL_1676740 Displacement of [3H]N-methyl-scopolamine from human recombinant muscarinic M1 receptor expressed in CHO-FlpIn cells after 6 hrs by liquid scintillation counting method
- ChEMBL_1676741 Displacement of [3H]N-methyl-scopolamine from human recombinant muscarinic M2 receptor expressed in CHO-FlpIn cells after 6 hrs by liquid scintillation counting method
- ChEMBL_1676742 Displacement of [3H]N-methyl-scopolamine from human recombinant muscarinic M3 receptor expressed in CHO-FlpIn cells after 6 hrs by liquid scintillation counting method
- ChEMBL_1676735 Displacement of [3H]N-methyl-scopolamine bromide from human recombinant muscarinic M1 receptor expressed in HEK293T cell membranes after 1 hr by liquid scintillation counting method
- ChEMBL_1676736 Displacement of [3H]N-methyl-scopolamine bromide from human recombinant muscarinic M2 receptor expressed in HEK293T cell membranes after 1 hr by liquid scintillation counting method
- ChEMBL_1676737 Displacement of [3H]N-methyl-scopolamine bromide from human recombinant muscarinic M3 receptor expressed in HEK293T cell membranes after 1 hr by liquid scintillation counting method
- Binding Assay Cell membrane proteins (Perkin Elmer) wherein human muscarinic M3 receptor was overexpressed, [3H]-methyl scopolamine and test compounds in various concentration were cultured in 0.2 ml of Tris-HCl buffer at 25° C. for 120 minutes. The same was filtered under suction through glass fiber filter (Whatman GF/B), and then the filter was washed 5 times with 1 ml of Tris-HCl buffer. The radioactivity of [3H]-methyl scopolamine adsorbed on the filter was measured by a liquid scintillation counter. Non-specific binding was evaluated under existence of 5 μM of atropine. Affinity of the compound of the present invention to muscarinic M3 receptor was calculated as the dissociation constant (Ki), which can be calculated from concentration (IC50) of test compounds inhibiting 50% of binding of [3H]-methyl scopolamine (i.e. labeled ligand) according to Cheng and Prusoff [Cheng and Prusoff, Biochem. Pharmacol., 22, 3099, 1973]. In following Table, compounds having stronger binding affinity to human muscarinic M3 receptor have lower dissociation constant (Ki).
- Muscarinic 3 Receptor Binding Assay The muscarinic 3 receptor binding assay was adapted from Perkin Elmer. Briefly, assay buffer (60 μL of pH 7.4 phosphate saline buffer) was added to polypropylene round bottom 96-well microtiter plates, followed by CHO cell suspension expressing the human M3 receptor (1 mg suspension/ml; 20 ug membrane suspension per well). 3H-Scopolamine (20 μL of a 7.5 nM solution) was added to each well and plates were shaken at room temperature for 2 h. Atropine (Sigma-Aldrich, St. Louis, Mo.) was used as a positive control. Test compounds and control samples were prepared in DMSO (20 mM) and diluted to give a final concentration of 20 μM. The reaction mixtures were then added to matrix 96-well GFC filtration microtiter plates that had been previously pretreated with 0.5% polyethylimine (100 μL) for 4 h and filtered. The binding reactions were terminated by filtering through the GFC plates and washing & filtering with ice-cold phosphate saline buffer (5×100 μL). Once the filters were dry, microscint scintillation cocktail (100 μL) was added to each well, allowed to sit for 20 min and the plates analyzed using a TopCount scintillation counter. Test compounds which showed >50% reduction in 3H-scopolamine binding at a final concentration of 20 μM were subjected to further serial dilutions and evaluated at various concentrations to determine their IC50 value. Curve fitting of % inhibition versus concentration using Excell software allowed determination of IC50 values for test compounds.
- Radioligand Binding Assay Radioligand binding assays for cloned muscarinic receptors were performed in 96-well microtiter plates in a total assay volume of 100 uL. CHO cell membranes stably expressing either the hM1, hM2, hM3, hM4 or hM5 muscarinic subtype were diluted in assay buffer to the following specific target protein concentrations (ug/well): 10 ug for hM1, 10-15 ug for hM2, 10-20 ug for hM3, 10-20 ug for hM4, and 10-12 ug for hM5 to get similar signals (cpm). The membranes were briefly homogenized using a Polytron tissue disruptor (10 seconds) prior to assay plate addition.Saturation binding studies for determining KD values of the radioligand were performed using L-[N-methyl-3H]scopolamine methyl chloride ([3H]-NMS) (TRK666, 84.0 Ci/mmol, Amersham Pharmacia Biotech, Buckinghamshire, England) at concentrations ranging from 0.001 nM to 20 nM.Displacement assays for determination of Ki values of test compounds were performed with [3H]-NMS at 1 nM.
- M3 Binding Assay Human M3 receptor membranes (15 μg/well) from Perkin Elmer are incubated with 0.52 nM Scopolamine Methyl Chloride, [N-methyl-3H] with or without test compounds, or a saturating concentration of Atropine (5 μM) for the determination of non-specific binding. The assay is carried out in 96-well polypropylene plates in a volume of 250 μl. The assay buffer used is 50 mM Tris-HCl, 154 mM NaCl (pH 7.4). The final assay concentration of DMSO is 0.5% (v/v). The plates are sealed and incubated for 2 h at room temperature on an orbital shaker (slow speed). Membranes are harvested onto 96-well unifilter GF/C filter plates pre-treated with 0.5% polyethyleneimine (v/v), using a filter manifold, washed four times with 200 μl of assay buffer. The plates are dried before addition of 50 μl of microscint-0, sealed then read in a Trilux Microbeta scintillation counter. IC50 values are determined from competition curves using a non-linear curve fitting program. Ki values are calculated from IC50 values by the Cheng and Prusoff equation.
- Radioligand Binding Assay Human M3 receptor membranes (15 μg/well) from Perkin Elmer are incubated with 0.52 nM Scopolamine Methyl Chloride, [N-methyl-3H] with or without test compounds, or a saturating concentration of Atropine (5 μM) for the determination of non-specific binding. The assay is carried out in 96-well polypropylene plates in a volume of 250 μl. The assay buffer used is 50 mM Tris-HCl, 154 mM NaCl (pH 7.4). The final assay concentration of DMSO is 0.5% (v/v). The plates are sealed and incubated for 2 h at room temperature on an orbital shaker (slow speed). Membranes are harvested onto 96-well unifilter GF/C filter plates pre-treated with 0.5% polyethyleneimine (v/v), using a filter manifold, washed four times with 2000 of assay buffer. The plates are dried before addition of 50 μl of microscint-0, sealed then read in a Trilux Microbeta scintillation counter. IC50 values are determined from competition curves using a non-linear curve fitting program. Ki values are calculated from IC50 values by the Cheng and Prusoff equation.
- Radioligand Binding Assay Radioligand binding assays for cloned muscarinic receptors were performed in 96-well microtiter plates in a total assay volume of 100 μL. CHO cell membranes stably expressing either the hM1, hM2, hM3, hM4 or hM5 muscarinic subtype were diluted in assay buffer to the following specific target protein concentrations (μg/well): 10 μg for hM1, 10-15 μg□for hM2, 10-20 μg□for hM3, 10-20 μg□for hM4, and 10-12 μg□for hM5 to get similar signals (cpm). The membranes were briefly homogenized using a Polytron tissue disruptor (10 seconds) prior to assay plate addition. Saturation binding studies for determining KD values of the radioligand were performed using L-[N-methyl-3H]scopolamine methyl chloride ([3H]-NMS) (TRK666, 84.0 Ci/mmol, Amersham Pharmacia Biotech, Buckinghamshire, England) at concentrations ranging from 0.001 nM to 20 nM. Displacement assays for determination of Ki values of test compounds were performed with [3H]-NMS at 1 nM and eleven different test compound concentrations. The test compounds were initially dissolved to a concentration of 400 μM in dilution buffer and then serially diluted 5× with dilution buffer to final concentrations ranging from 10 pM to 100 μM. The order of addition and volumes added to the assay plates were as follows: 25 μL radioligand, 25 μL diluted test compound, and 50 μL membranes. Assay plates were incubated for 6 hours at 37° C. Binding reactions were terminated by rapid filtration over GF/B glass fiber filter plates (PerkinElmer, Inc.) pre-treated in 1% BSA. Filter plates were rinsed three times with wash buffer (10 mM HEPES) to remove unbound radioactivity. The plates were then air-dried and 50 μL Microscint-20 liquid scintillation fluid (PerkinElmer, Inc.) were added to each well. The plates were then counted in a PerkinElmer Topcount liquid scintillation counter (PerkinElmer, Inc.).