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.
Tanaka
Y
Y
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Morimoto
K
K
Ishii
K
K
Nakayama
K
K
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014749:Vincamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011956:Receptors, Cell Surface; D014665:Vasodilator Agents; D014749:Vincamine; C033581:11-bromovincamine; D004110:Diltiazem; D011188:Potassium; D002118:Calcium