Blockade of human atrial 5-HT4 receptors by GR 113808.
1. The mode of antagonism of 5-hydroxytryptamine (5-HT)-induced positive inotropic effects by the highly selective 5-HT4 receptor antagonist GR 113808 ([1-[2-methylsulphonylamino ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate) was investigated on isolated preparations of human right atrium. 2. GR 113808 caused concentration-dependent (2-100 nM) surmountable antagonism of the effects of 5-HT with a pKB (M) of 8.8. 3. The affinity of GR 113808 for human atrial 5-HT4 receptors, together with its high selectivity for 5-HT4 receptors comprise useful properties for investigating the question of 5-HT4 receptor subtypes.
Kaumann
A J
AJ
Clinical Pharmacology Unit, Cambridge University, Addenbrooke's Hospital.
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000648:ultrastructure; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology*
D002316:Cardiotonic Agents; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C082871:GR 113808