Effects of VA-045, a novel apovincaminic acid derivative, on isolated blood vessels: Cerebroarterial selectivity

Abstract 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 (3×10 −9 −3×10 −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.