Effects of VA-045, a novel apovincaminic acid derivative, on isolated blood vessels: cerebroarterial selectivity.
We investigated the effects of VA-045, an apovincaminic acid derivative, on isolated blood vessels. VA-045 (10(-7)-10(-5) M) and vinpocetine (10(-7)-10(-5) M) inhibited the 64 mM KCl-induced and 10(-6)M norepinephrine (NE)-induced contraction of rat aortic strips. VA-045 (10(-7)-10(-4) M) and vinpocetine (10(-7)-10(-4) M) inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterase in porcine coronary artery. VA-045 (3 x 10(-9-3 x 10(-6) M) relaxed the 64 mM KCl-induced contraction of the canine basilar artery without affecting the peripheral arteries. These results indicate that VA-045 selectively dilates canine cerebral artery, and that it may be a useful agent for the treatment of cerebrovascular diseases such as stroke.
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
N
N
Miyata
H
H
Yamaura
M
M
Tanaka
M
M
Muramatsu
K
K
Tsuchida
S
S
Okuyama
S
S
Otomo
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; C013983:vinpocetine; D011189:Potassium Chloride; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D009638:Norepinephrine