Cardiovascular pharmacology of cinepazide, a new cerebral vasodilator

Cardiovascular effects of cinepazide were compared with those of cinnarizine and papaverine. Cinepazide (3-30 mg/kg, i.v.)produced a dose-related and transient increase in vertebral, carotid, renal and femoral arterial flow as well as cardiac output and a decrease in total peripheral resistance in anesthetized dogs. The magnitude and duration of mesenteric vasodilatation induced by cinepazide was much greater as compared to other vascular effects, and these effects were associated with a prolonged hypotension. The drug exerted positive inotropic and chronotropic actions, the latter being followed by bradycardia with the highest dose. Cinnarizine(0.3-3 mg/kg, i.v.)produced a greater increase in vertebral blood flow with bradycardia and papaverine(0.1-1 mg/kg, i.v.)produced a remarkable carotid vasodilatation with cardiac stimulation. Both reference drugs decreased renal blood flow. Cinepazide (30 mg/kg, i.v.)potentiated the vertebral vasodilator response of dogs to intravertebral adenosine and cyclic AMP, while cinnarizine (3 mg/kg i.v.) reduced their vasodilator effects. Intravertebral cinepazide(1-10 mg), like cinnarizine(0.1-1 mg) and papaverine (0.1-1 mg), increased vertebral blood flow in a dose-related manner and the effect was partially inhibited by intravenous pretreatment with aminophylline but not by pretreatment with autonomic antagonists. These antagonists did not modify the cinnarizine effect. Cinepazide resembled cinnarizine and papaverine in that the drug antagonized rabbit aortic contraction induced by KCl, norepinephrine or CaCl2.