GR127935 is a potent antagonist of the 5-HT1-like receptor mediating contraction in the canine coronary artery.
The effects of the recently developed 5-HT1D receptor antagonist, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1,-biphenyl]-4-carboxamide), and those of the preferential human 5-HT1D alpha receptor antagonist, ketanserin, on the isometric contraction induced by 5-hydroxytryptamine (5-HT) and sumatriptan in endothelium-denuded ring segments of canine coronary artery were analyzed. Sumatriptan mimicked 5-HT with lower potency but similar efficacy. GR127935 (1,3 and 10 nM) concentration dependently antagonized the contractions elicited by both agonists; only the 5-HT maximum was reduced. Ketanserin and mianserin (both at 1 microM) were inactive. These data strongly suggest that a 5-HT1D receptor mediates contraction in the dog coronary artery. The possibility that this 5-HT1D receptor resembles the cloned human 5-HT1D beta subtype is discussed.
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Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, México, D.F., Mexico.
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D007650:Ketanserin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090701:GR 127935; D012701:Serotonin; D018170:Sumatriptan; D007650:Ketanserin