Flunarizine, an anti-migraine agent, impairs nitroxidergic nerve function in cerebral arteries.
Flunarizine is an anti-migraine agent that blocks the Ca2+ entry across cell membrane. In order to obtain a clue of mechanisms underlying the migraine headache, modifications by flunarizine of the response to nitric oxide (NO), a cerebral vasodilator and algogenic agent, derived from perivascular nerves were evaluated. Relaxations due to nerve stimulation by electrical pulses (5 Hz) and nicotine (10(-4) M) in canine cerebral arterial strips were attenuated by treatment with flunarizine dose-dependently, whereas the responses to exogenous NO (10(-7)-10(-6) M) and nitroprusside (10(-8)-10(-6) M) were unaffected. The inhibition by the Ca2+ entry blocker of the response to electrical nerve stimulation and nicotine was obtained in a concentration (10(-6) M) that did not significantly relax the arterial strips. NO derived from perivascular nerve may be one of the factors involved in the genesis of migraine attack, which is expected to be relieved by a reduction of neural NO synthase activity associated with a decreased Ca2+ influx by flunarizine during nerve activation.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Sciences, Seta, Ohtsu, Japan.
Okamura
T
T
Toda
N
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002536:Cerebral Arteries / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005444:Flunarizine / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009599:Nitroprusside; D009569:Nitric Oxide; D009538:Nicotine; D005444:Flunarizine