PHARMACODYNAMICS AND DRUG ACTION Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model Background andpwpose: Sumatrlptan is a selective5hydroxytryptamine,, (5HT,,)-receptor agonist, highly effective in tbe short-term treatment of migraine headaches. However, the mechanism underlying the action of sumatiptan is not yet completely understood. To further cbaracrerize the vascular effects of sumarriptan, we studied tbe effects on cerebral and ocular circulation in the well-established nitroglycerin headachemodel. Methods: In a double-blind, placebo-controlled, randomized, two-way crossover study in 10 healthy male subjects, we administered either placebo plus nitroglycerin or sumatriptan plus nitroglycerin. Blood flow velocity in the middle cerebral artery and the ophthalmic artery, as well as ocular fundus pulsations and systemic hemodynamic parameters, were measured after suxnatriptan and placebo and during tbe follow- ing infusion of nitroglycerin. Results: After infusion of nitroglycerin, blood flow velocity in the middle cerebral decreased by -13.3% versus baseline after placebo pretreatment, but by only -2.2% after sumatriptan (treatment effect, +lO.S%; p < 0.05). In contrast, sumatriptan had no effect in the ophthalmic artery. Ocular fundus pulsations, which estimate local pulsatile ocular blood flow, were slightly reduced after sumatriptan. Moreover, sumatriptan partially prevented tbe increase in fundus pulsations during nitroglycerin infusion (treatment effect, -5.4%; p < 0.05). Concl~ssiorzs: Sumatriptan prevents the effect of nitroglycerin-induced vasodilation in the middle cerebral artery but not in the ophthalmic artery, which strongly supports the concept that sumatriptan directly vasoconstricts distended basal cerebral arteries. Measurement of ocular fundus pulsations indicates that sumatriptan also has a small vasoconstrictor action on resistance vessels. (Clin Pharmacol Ther 1996;60: 199-205.) Leopold Schmetterer, PhD, Michael Wolzt, MD, Kurt Krejcy, MD, Ursula Graselli, RN, Oliver Findl, MD, Hans-Georg Eichler, MD, and Ernst A. Singer, MD Vienna, Austria Sumatriptan is a selective 5hydroxytryptamine,, (5-I-IT,,)-receptor agonist that is highly effective in the short-term treatment of migraine headaches,172 From the Department of Clinical Pharmacology, the Institute of Medical Physics, the Institute of Pharmacology,and the Depart- ment of Ophthalmology, Vienna University School of Medicine. Received for publication Dec. 21,1995; accepted March 11,1996. Reprint request: Leopold Schmetterer, PhD, Institute of Medical Physics, WHhringer Strasse 13, A-1090, Vienna, Austria. Copyright 0 1996 by Mosby-Year Book, Inc. 0009-9236/96/$5.00 + 0 13/l/73452 with a low abuse potential.3 After subcutaneous in- jection with 6 mg sumatriptan, more than 80% of the patients showed improvement in the severity of symptoms within 2 hours.4 The mechanism underlying the action of sumatriptan is not yet completely understood. Both cranial vasoconstriction5,6 and inhibition of calcito- nin gene-related peptide release caused by stimula- tion of the trigeminal system7 have been proposed. A vasoactive effect would be compatible with the vascular hypothesis of migraine, suggesting that va- 199