Query String: CARBACHOL
CARBACHOL 2-[(AMINOCARBONYL)OXY]-N,N,N-TRIMETHYLETHANAMINIUM BDBM50014555 CHEMBL965 Miostat Carbastat
2-(carbamoyloxy)-N,N,N-trimethylethanaminium Carbachol chloride (2-Hydroxyethyl)trimethylammonium chloride carbamate (carbachol)(2-Carbamoyloxy-ethyl)-trimethyl-ammonium (2-Hydroxyethyl)trimethyl ammonium chloride carbamate CARBASTAT Karbamoylcholin chlorid Choline chloride, carbamate Choline chlorine carbamate CHEMBL14 (2-Carbamoyloxyethyl)trimethylammonium chloride CARBACHOL 2-(carbamoyloxy)-N,N,N-trimethylethanaminium chloride BDBM50004656 Carbamylcholine MIOSTAT Choline carbamate chloride Karbachol (2-Carbamoyloxy-ethyl)-trimethyl-ammonium 2-((Aminocarbonyl)oxy)-N,N,N-trimethylethanaminium chloride 2-((Aminocarbonyl)oxy)-N,N,N-trimethylethanaminum chloride
- ChEMBL_3326 (CHEMBL619026) In vitro relaxation of carbachol pre-contracted rat oesophageal TMM.
- ChEMBL_1972414 (CHEMBL4605232) Antagonist activity at human muscarinic M3 receptor expressed in HEK293 assessed as inhibition of carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition and measured after 90 mins by TR-HTRF assay
- ChEMBL_1350971 (CHEMBL3268500) Agonist activity at human 5-HT3A receptor expressed in HEK293 cells in presence of carbachol
- ChEMBL_1350972 (CHEMBL3268501) Agonist activity at mouse 5-HT3A receptor expressed in HEK293 cells in presence of carbachol
- ChEMBL_2099973 (CHEMBL4808369) Inhibition of Galphaq/11 (unknown origin) expressed in CHO cells coexpressing M1 receptor assessed as reduction in carbachol-induced IP1 accumulation preincubated for 1 hr followed by carbachol stimulation and measured after 1 hr by HTRF assay
- ChEMBL_2150080 (CHEMBL5034542) Antagonist activity at muscarinic M3 receptor in rat trachea assessed as inhibition of carbachol-induced contraction
- ChEMBL_2279657 Binding affinity to human muscarinic M3 receptor expressed in human HEK293T cells assessed as inhibition of carbachol-induced G-protein signaling by measuring inositol accumulation preincubated for 30 mins followed by carbachol stimulation and measured after 90 mins by HTRF assay
- ChEMBL_1520149 (CHEMBL3625721) Agonist activity at human NTS1 in Sprague-Dawley rat ileum assessed as inhibition of carbachol-induced contraction
- ChEBML_1698018 Antagonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced RLuc8-fused Galphaq activation preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
- ChEMBL_1698018 (CHEMBL4048908) Antagonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced RLuc8-fused Galphaq activation preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
- ChEMBL_1698023 (CHEMBL4048913) Antagonist activity at human SP/Myc epitope-tagged muscarinic M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced RLuc8-fused Galphaq activation preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
- ChEMBL_1895768 (CHEMBL4397803) Antagonist activity at human muscarinic M2 receptor expressed in HEK293 cells co-expressing HA-Galphaq/i5 assessed as inhibition of carbachol-induced IP1 accumulation pre-incubated for 30 mins followed by carbachol addition and measured after 1 hr by HTRF assay
- ChEMBL_2279658 Binding affinity to human muscarinic M3 receptor expressed in human HEK293T cells cells co-expressing beta-arrestin2 assessed as inhibition of carbachol-induced beta-arrestin recruitment preincubated for 30 mins followed by carbachol stimulation and measured after 90 mins by PathHunter assay
- ChEMBL_1541151 (CHEMBL3744760) Agonist activity at 5-HT4 receptor in Sprague-Dawley rat oesophagus assessed as relaxation of carbachol precontracted oesophagus
- ChEMBL_1552716 (CHEMBL3762973) Agonist activity at 5-HT4 receptor in rat esophageal thoracic muscularis mucosae assessed as carbachol-induced contraction
- ChEMBL_1698020 (CHEMBL4048910) Antagonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced mVenus-fused beta-arrestin2 recruitment preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
- ChEMBL_1698025 (CHEMBL4048915) Antagonist activity at human SP/Myc epitope-tagged muscarinic M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced mVenus-fused beta-arrestin2 recruitment preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
- ChEMBL_1972417 (CHEMBL4605235) Antagonist activity at muscarinic M3 receptor (unknown origin) expressed in HEK293 cells coexpressing EA tagged beta-arrestin2 assessed as inhibition of carbachol-induced beta-arrestin2 recruitment preincubated for 30 mins followed by carbachol addition and measured after 90 mins by PathHunter assay
- ChEMBL_3332 (CHEMBL619032) 5-hydroxytryptamine 4 receptor agonist activity was determined by the relaxation of the carbachol-contracted rat esophageal tunica muscularis mucosae
- ChEMBL_429190 (CHEMBL913824) Activity at muscarinic M3 receptor in Albino Dunkin-Hartley guinea pig trachea assessed as inhibition of carbachol-induced contraction
- ChEMBL_1972531 (CHEMBL4605349) Antagonist activity at human muscarinic M2 receptor expressed in HEK293 cells co-expressing HA-Galphaq/i5 assessed as inhibition of carbachol-induced IP1 accumulation at 37 degree C pre-incubated for 30 mins followed by carbachol addition and measured after 60 mins by HTRF assay
- ChEMBL_1700406 (CHEMBL4051388) Competitive antagonist activity at human muscarinic acetylcholine receptor M2 expressed in HEK293 cells coexpressing HA tagged Galpha-protein qi5 assessed as inhibition of 0.1 uM carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition measured after 1 hr by HTRF assay
- ChEMBL_1700407 (CHEMBL4051389) Competitive antagonist activity at human muscarinic acetylcholine receptor M2 expressed in HEK293 cells coexpressing HA tagged Galpha-protein qi5 assessed as inhibition of 1 uM carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition measured after 1 hr by HTRF assay
- ChEMBL_1700408 (CHEMBL4051390) Competitive antagonist activity at human muscarinic acetylcholine receptor M2 expressed in HEK293 cells coexpressing HA tagged Galpha-protein qi5 assessed as inhibition of 10 uM carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition measured after 1 hr by HTRF assay
- ChEMBL_446233 (CHEMBL895338) Agonist activity at adrenergic beta-2 receptor in guinea pig tracheal rings assessed as myorelaxing activity on carbachol-induced contraction
- ChEMBL_1972538 (CHEMBL4605356) Antagonist activity at human muscarinic M2 receptor expressed in HEK293 cells co-expressing HA-Galphaq/i5 assessed as inhibition of carbachol-induced IP1 accumulation at 22 degree C pre-incubated for 180 mins followed by carbachol addition and further incubated at 37 degree C for 90 mins by HTRF assay
- ChEMBL_1972539 (CHEMBL4605357) Antagonist activity at human muscarinic M4 receptor expressed in HEK293 cells co-expressing HA-Galphaq/i5 assessed as inhibition of carbachol-induced IP1 accumulation at 22 degree C pre-incubated for 180 mins followed by carbachol addition and further incubated at 37 degree C for 90 mins by HTRF assay
- ChEMBL_1439178 (CHEMBL3386127) Antagonist activity at human M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by beta-arrestin engagement assay
- ChEMBL_1875664 (CHEMBL4377058) Inhibition of human TRPC3 expressed in HEK293 cells assessed as reduction in carbachol-induced membrane potential by FMP-2 dye based assay
- ChEMBL_446228 (CHEMBL895333) Agonist activity at adrenergic beta2 receptor in guinea pig tracheal rings assessed as myorelaxing activity on carbachol-induced contraction in presence of propranolol
- ChEMBL_577488 (CHEMBL1057071) Agonist activity at adrenergic beta2 receptor in Hartley guinea pig tracheal ring assessed as bronchorelaxation activity against carbachol-induced contraction
- ChEMBL_1801541 (CHEMBL4273833) Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay
- ChEMBL_201191 (CHEMBL801210) Compound was tested against 5-HT4 receptor through agonism of 5-HT mediated relaxation of rat, carbachol contracted esophageal muscularis mucosae
- ChEMBL_477429 (CHEMBL929415) Antagonist activity at human muscarinic M4 receptor expressed in CHO cells assessed as blockade of carbachol-induced inhibition of forskolin-stimulated cAMP accumulation
- ChEMBL_138159 (CHEMBL748223) Inhibition of carbachol-induced release of alpha-amylase from pancreatic acinar cells from that of rat ileum contained the muscarinic acetylcholine receptor M2 subtypes
- ChEMBL_1438420 (CHEMBL3383649) Antagonist activity at human M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by BRET based Gq protein engagement assay
- ChEMBL_1438428 (CHEMBL3384240) Antagonist activity at human M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by BRET based Gq protein activation assay
- ChEMBL_1439162 (CHEMBL3385563) Antagonist activity at human M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by BRET based beta-arrestin engagement assay
- ChEMBL_1439168 (CHEMBL3386117) Antagonist activity at human M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by BRET based Gq protein engagement assay
- ChEMBL_1439174 (CHEMBL3386123) Antagonist activity at human M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced response by BRET based Gq protein activation assay
- ChEMBL_1856734 (CHEMBL4357463) Inhibition of Gq-mediated signalling in CHOK1 cells stably expressing M1 muscarinic receptor assessed as inhibition of carbachol-induced IP1 production by HTRF assay
- ChEMBL_2216709 (CHEMBL5129841) Invivo antagonist activity at muscarinic M3 receptor activity in Dunkin-Hartley guinea pig trachea assessed as inhibition of carbachol induced contraction in presence of propranolol
- ChEMBL_978640 (CHEMBL2422303) Inhibition of human recombinant TRPC6 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay
- ChEMBL_978642 (CHEMBL2422305) Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay
- ChEMBL_1438422 (CHEMBL3383651) Positive modulatory activity at human M1 receptor expressed in HEK293T cells assessed as effect on carbachol-induced response by BRET based Gq protein engagement assay
- ChEMBL_1439156 (CHEMBL3385557) Positive modulatory activity at human M1 receptor expressed in HEK293T cells assessed as effect on carbachol-induced response by BRET based Gq protein activation assay
- ChEMBL_1929752 (CHEMBL4432928) Activation of p75NTR in C57BL/6 mouse brain assessed as suppression of carbachol-mediated persistant firing of entorhinal cortex after 15 mins by current-clamp technique
- ChEMBL_756378 (CHEMBL1805404) Agonist activity at human M1 muscarinic receptor expressed in CHO cells assessed as inhibition of carbachol-stimulated phosphatidyl-inositol hydrolysis by cell-based functional assay
- ChEMBL_1526363 (CHEMBL3637424) Antagonist activity at human muscarinic M3 receptor expressed in HEK293 cells assessed as inhibition of carbachol-induced inositol monophosphate accumulation after 1 hr by FRET assay
- ChEMBL_1875663 (CHEMBL4377057) Inhibition of mouse TRPC6 expressed in HEK293 cells co-expressing M5 receptor assessed as reduction in carbachol-induced membrane potential by FMP-2 dye based assay
- ChEMBL_1278646 (CHEMBL3095634) Antagonist activity at human M3 receptor expressed in CHO cells assessed as inhibition of carbachol-induced response after 30 mins by AP-1-driven luciferase reporter gene assay
- ChEMBL_882202 (CHEMBL2215475) Antagonist activity at EGFP-fused human M1 receptor N-terminal truncated at 17 residues expressed in HEK293 cells assessed as inhibition of carbachol induced calcium response by fluorescence assay
- ChEMBL_446227 (CHEMBL895332) Agonist activity at adrenergic beta-2 receptor in guinea pig tracheal rings assessed as myorelaxing activity on carbachol-induced contraction in presence of 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one
- ChEMBL_790183 (CHEMBL1925523) Positive allosteric modulation of rat mGlu4 receptor expressed in human HEK293 cells co-expressing GIRK potassium channels assessed as potentiation of carbachol-induced thallium flux measured between 10 to 20 secs
- ChEMBL_1875686 (CHEMBL4377080) Inhibition of YFP-tagged mouse TRPC4 beta expressed in thapsigargin treated HEK293 cells co-expressing M3 receptor assessed as reduction in carbachol-induced calcium level by fluo-4 dye based fluorescence assay
- [3H]NMS/Carbachol Binding Assay In brief, binding reactions containing ~10 μg of membrane protein per tube were carried out for 2 h (22 °C) in 1 ml of binding buffer containing 25 mM sodium phosphate and 5 mM MgCl2 (pH 7.4). In saturation binding assays, we employed six different [3H]NMS concentrations (200 to 7,000 pM). In competition binding assays, we used a fixed concentration of [3H]NMS (500 pM) in the presence of 10 different concentrations of carbachol, the cold competitor. Nonspecific binding was defined as binding observed in the presence of 10 μM atropine. Binding reactions were terminated by rapid filtration over GF/C Brandel filters, followed by three washes (~4 ml/wash) with ice-cold distilled water. The amount of radioactivity that remained bound to the filters was determined by liquid scintillation spectrometry.
- In Vitro Cellular Assay Following agonist data acquisition, cells were then incubated for a further 30 min at room temperature before either an EC20 concentration (to measure positive allosteric modulator activity) or an EC50 concentration (to measure antagonism) of carbachol was added using a fluorometric imaging plate reader. Positive allosteric modulator pEC50 values and antagonist pIC50 values for each compound were then determined. PAM Emax values were generated following normalisation between the EC20 base line fluorescence (0%) and maximal carbachol effect (100%). Antagonist Emax values were generated following normalisation between the EC80 fluorescence (0%) and baseline EC0 (DMSO) response (100%). Data analysis was carried out using a 4 parameter logistic nonlinear regression model with the XLFIT (IDBS) excel add-in10. 1-10 Examples 76-80 and 82-89 were tested in a slightly modified procedure. The points of modification and the alternate reagents, concentrations or equipment employed in these examples were: 1200 μg/ml hygromycin B; 2G418 not added; 3CELLBANKER 1; 410E6; 5 40 μl; 6 1 in 99; 7 20 μl; 8FDSS6000 (Hamamatsu Photonics); 9(480Ex, 540Em); 10Spotfire (TIBCO).As measured by the above in vitro assay, compound Examples 1 to 105 are positive allosteric modulators of mAChR M1 displaying the pEC50 values for positive allosteric modulation given in Table 2.
- [35S]GTPγS Binding/Immunoprecipitation Assay In brief, membranes from COS-7 cells expressing different Cys-substituted mutant M3R constructs were first treated with CuPhen (100 μM; 10 min at 37 °C). Control samples were incubated under the same experimental conditions in the absence of CuPhen. Subsequently, receptor-containing membranes (75 μg of protein) were incubated with the muscarinic agonist, carbachol (1 mM) for 2 min at 30 °C in the presence of 1 nM [35S]GTPγS. Following membrane solubilization and pre-clearing, Gαq/11 proteins were immunoprecipitated with a selective anti-Gαq/11-specific antiserum as described [Akam et al., Br. J. Pharmacol., 132:950-958]. Nonspecific binding was determined in the presence of 10 μM GTPγS.