Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model.
OBJECTIVE
Sumatriptan is a selective 5-hydroxytryptamine1d (5-HT1d)-receptor agonist, highly effective in the short-term treatment of migraine headaches. However, the mechanism underlying the action of sumatriptan is not yet completely understood. To further characterize the vascular effects of sumatriptan, we studied the effects on cerebral and ocular circulation in the well-established nitroglycerin headache model.


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 sumatriptan and placebo and during the following 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, +10.8%; 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 the increase in fundus pulsations during nitroglycerin infusion (treatment effect, -5.4%; p < 0.05).


CONCLUSIONS
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.
Schmetterer
L
L
Department of Clinical Pharmacology, Vienna University School of Medicine, Austria.
Wolzt
M
M
Krejcy
K
K
Graselli
U
U
Findl
O
O
Eichler
H G
HG
Singer
E A
EA
D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D006261:Headache / Q000139:chemically induced / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D005996:Nitroglycerin / Q000037:antagonists & inhibitors*; D009880:Ophthalmic Artery / Q000187:drug effects*; D012016:Reference Values; D012171:Retinal Vessels / Q000187:drug effects; D018170:Sumatriptan / Q000008:administration & dosage / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D018170:Sumatriptan; D005996:Nitroglycerin