EFFECT OF SUMATRIPTAN, A SELECTIVE 5-HT(1)-LIKE RECEPTOR AGONIST, ON PIAL VESSEL DIAMETER IN ANESTHETIZED CATS

The action of sumatriptan, a selective 5-HT1-like receptor agonist that is effective for the acute treatment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10-mu-M), when microinjected perivascularly, caused a decrease in pial artery diameter (maximum change of -19 +/- 9%; mean +/- SD) but had no effect on the diameter of pial veins. Sumatriptan (1-mu-M)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (1-mu-M) or ondansetron (1-mu-M but was significantly (p < 0.01) attenuated by methiothepin (1-mu-M). Intravenous infusion of a clinically effective dose of sumatriptan (64-mu-g/kg/10 min) caused selective carotid vasoconstriction (22 +/- 6% increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (1-mu-M) administered perivascularly in these animals before and after the infusion caused pial artery vasoconstriction. These results demonstrate that perivascularly administered sumatriptan causes pial artery vasoconstriction via activation of 5-HT1-like receptors. However, intravenously administered sumatriptan does not cause pial artery vasoconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.