Calcium antagonistic vasodilator mechanisms of brovincamine fumarate studied in canine cerebral artery.

In order to elucidate the major mechanism of cerebral vasodilator action of brovincamine fumarate (CAS 57475-17-9) the present study was performed comparing its effects with those of d-cis-diltiazem in the isolated canine basilar artery. Brovincamine possessed a wide spectrum of inhibitory actions on the contractions of the artery produced by various spasmogens and mechanical stretch. Brovincamine was 3 to 40 times less potent than d-cis-diltiazem in the inhibitory actions. Simultaneous recordings of intracellular Ca2+ concentration and mechanical activity showed that brovincamine and d-cis-diltiazem decreased both parameters augmented by high KCl in a concentration-dependent and parallel manner. Both brovincamine and d-cis-diltiazem shifted parallel to the right the concentration-response curves for CaCl2-induced contraction of the artery constructed in the Ca(2+)-free depolarizing medium. Furthermore, Schild regression of the curves was linear with a slope of unity, indicating apparently a competitive antagonism between Ca2+ channel function/Ca2+ and brovincamine or d-cis-diltiazem. The results suggest that the cerebral vasodilator effect of brovincamine is mainly attributable to the inhibition of Ca2+ influx through the voltage-dependent Ca2+ channels, supporting the reported clinical benefits of this drug in the treatment of cerebrovascular disorders.