Abstract
1. MK-462 (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H- indol-3-yl]ethylamine) is a novel selective 5-HT1D-receptor agonist which in clinical trials has been shown to be an effective antimigraine agent. As angiographic studies have shown that sumatriptan (an established 5-HT1D-receptor agonist) can cause coronary artery vasoconstriction in patients, we compared the effects of MK-462 with those of 5-HT and those of sumatriptan, on isolated segments of human coronary artery in vitro. 2. Coronary arteries were obtained from explanted hearts from patients (n = 22, 2 females, 20 males, aged 21-60 years) undergoing cardiac transplantation. Endothelium-denuded ring segments of coronary artery, 2mm long were mounted in organbaths for isometric tension recording. For each arterial ring segment, a cumulative concentration-effect curve to either 5-HT, sumatriptan or MK-462 was determined. After maximal response to each agonist had been obtained, ketanserin (a 5-HT2 receptor antagonist) 0.6 microM was added to the tissue bath, followed by methiotepin (0.6 microM) and the reduction in tension produced by the addition of each antagonist was determined. 3. Out of 22 coronary arteries studied, only 10 showed any response (contraction) to 5-HT. Not all arteries which responded to 5-HT contracted in response to both sumatriptan and MK-462 (one ring from each artery being exposed to a single agonist in each case).(ABSTRACT TRUNCATED AT 250 WORDS)