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

Abstract

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.

• Authors: Y Tanaka, K Morimoto, K Ishii, K Nakayama
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 44 Issue 7 Pg. 803-8 (Jul 1994) ISSN: 0004-4172 [Print] Germany
• PMID: 7945512 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Receptors, Cell Surface
• Vasodilator Agents
• Vincamine
• 11-bromovincamine
• Diltiazem
• Potassium
• Calcium

Topics

• Animals
• Basilar Artery (drug effects, metabolism, physiology)
• Calcium (metabolism, pharmacology)
• Calcium Channel Blockers (pharmacology)
• Cell Membrane (drug effects)
• Cerebral Arteries (drug effects, metabolism, physiology)
• Diltiazem (pharmacology)
• Dogs
• Female
• In Vitro Techniques
• Isometric Contraction (drug effects)
• Male
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Potassium (pharmacology)
• Receptors, Cell Surface (drug effects)
• Vasodilator Agents (pharmacology)
• Vincamine (analogs & derivatives, pharmacology)