Summary: The action of sumatriptan, a selective 5-HT) like receptor agonist that is effective for the acute treat ment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10 /J-M), when mi croinjected perivascularly, caused a decrease in pial ar tery diameter (maximum change of -19 ± 9%; mean ± SD) but had no effect on the diameter of pial veins. Suma triptan (l /J-M)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (l /J-M) or ondansetron (l /J-M) but was significantly (p < 0.01) at tenuated by methiothepin (l/J-M). Intravenous infusion of a clinically effective dose of sumatriptan (64 /J-g/kg/l0 min) caused selective carotid vasoconstriction (22 ± 6% Sumatriptan (GR43175) is a novel, highly selec tive agonist for the 5-HT1-like receptor, which me diates vasoconstriction of certain blood vessels (Humphrey et aI., 1988). This 5-HT1 receptor sub type was first identified in dog isolated saphenous vein but appears to be largely restricted to intracra nial blood vessels (Humphrey et aI., 1988(Humphrey et aI., , 1990b. Thus, it has been shown that sumatriptan causes contraction of isolated large cerebral arteries from dog, primate, and humans (Connor et aI., 1989; Par sons et aI., 1989) and human isolated dural arteries (Humphrey et aI., 1990b) via activation of 5-HTJlike receptors but has little or no effect on tone in most peripheral isolated vascular preparations (Humphrey et aI., 1988). Similarly, in vivo, suma triptan selectively constricts the carotid vascular bed in anaesthetised dogs (Feniuk et aI., 1989) and cats (Perren et aI., 1989). This selective action of sumatriptan for the cranial vasculature reflects the Received April 15, 1991; final revision received October 10, 1991; accepted December 9, 1991.Address correspondence and reprint requests to Dr. H. E. Connor at Department of Neuropharmacology, Glaxo Group Re search Ltd., Park Road, Ware, Hertfordshire, SGl2 ODP, U. K.
514increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (l /J-M) admin istered 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 acti vation of 5-HTclike receptors. However, intravenously administered sumatriptan does not cause pial artery va soconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.
