Cardiac and haemodynamic effects of intravenous administrations of flunarizine in closed-chest anaesthetized mongrel dogs.
This study was performed to evaluate the cardiac and haemodynamic effects of 1-cinnamyl-4-[bis(p-fluorophenyl)methyl]piperazine dihydrochloride (flunarizine, Sibelium ). The compound was dissolved in distilled water acidified with tartaric acid in a concentration of 2 mg/ml (pH 1.8) and administered intravenously in cumulative doses of 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Flunarizine induced systemic vasodilatation dose- relatedly starting with a dose of 0.1 mg/kg i.v. as indicated by the decrease in systemic vascular resistance, while this compound had no vasodilating properties in the pulmonary circulation. Flunarizine caused an increase in heart rate following the administration of the higher doses. This effect is probably reflexogenic in nature and secondary to the decrease in aortic blood pressure. As a consequence the oxygen demand of the myocardium enhanced after these high doses of flunarizine as indicated by the increase in pressure-rate product. Flunarizine did not affect the contractility and the conduction of the heart in the doses of 0.03 up to and including 1.0 mg/kg i.v., but could have some negative inotropic properties at the highest dose used. The end-tidal CO2 concentration in the expired air increased after the administration of 0.3 up to and including 3.0 mg/kg i.v. From these results, it is concluded that flunarizine has systemic vasodilating properties without any cardiac effects at doses from 0.03 up to and including 1.0 mg/kg i.v.
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002936:Cinnarizine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D005444:Flunarizine; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D013997:Time Factors
D002121:Calcium Channel Blockers; D010879:Piperazines; D002245:Carbon Dioxide; D002936:Cinnarizine; D005444:Flunarizine