Protective effect of flunarizine against cerebral hypoxia-anoxia in mice and rats.
The protective effect of flunarizine against cerebral hypoxia-anoxia was investigated with various experimental models in mice and rats. The effect of flunarizine was compared with those of cinnarizine, verapamil and pentobarbital. The oral treatment of animals with flunarizine resulted in a consistent and long-lasting-protection against cerebral hypoxia-anoxia in all the models examined: Cytotoxic anoxia by KCN injection, hypercapnic anoxia induced by stopping artificial respiration, hypobaric hypoxia and normobaric hypoxia. The minimal effective dose of flunarizine was 1 to 20 mg/kg. The activity of flunarizine was 4 to 30 times as potent as that of cinnarizine and pentobarbital. Verapamil showed little or no protective effect. The mode of action of flunarizine was different from that of pentobarbital, which showed protection at anaesthetizing doses. These results indicate that flunarizine possesses a universal protective effect against cerebral hypoxia-anoxia, through the mechanism involved remains to be clarified. Hence, it is suggested that flunarizine might exert a beneficial effect on oxygen insufficiency of the brain resulting from cerebral ischemia.
D000818:Animals; D002936:Cinnarizine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D005444:Flunarizine; D002534:Hypoxia, Brain / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010424:Pentobarbital / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014700:Verapamil / Q000627:therapeutic use
D010879:Piperazines; D014665:Vasodilator Agents; D002936:Cinnarizine; D014700:Verapamil; D010424:Pentobarbital; D005444:Flunarizine