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.