Comparison of the Effects of Vinpocetine, Vincamine, Phenytoin, and Cinnarizine in a Rat Model of Cerebral lschemia

Gary A. King and Dolores Narcavage

Ayerst Laboratorias Research, Inc.,
CN 8000, Princeton, New Jersey
Drug Dev. Res. 9:225- 231,1986.

Abstract

Vinpocetine is an eburnamenine derivative reported to protect the brain from ischemia, both in experimental animals and in man. Its effects have been directly compared to those of vincamine, phenytoin, and cinnarizine in the Fisher rat following bilateral carotid artery occlusion (BCAO). Upon acute b.i.d. administration (25-100 rng/kg i.p.), both vinpocetine and vincamine significantly increased latency to ischemic convulsion in a dose-related manner, but neither drug significantly affected survival time. Neither phenytoin nor cinnarizine (25-100 mg/kg, b.i.d.) significantly altered latency to convulsions or survival time. After daily dosing for 5 days, vinpocetine, but none of the other drugs, caused a dose-related increase in the latency to ischemic convulsion. Vinpocetine’s effects occurred at lower doses (25 and 50 mg/kg/day) after subchronic administration than after acute administration. Vinpocetine (25 mg/kg/day) and cinnarizine (100 mg/kg/day) also increased survival time. These results are consistent with other experimental and clinical studies demonstrating a protective effect of vinpocetine against cerebral ischemia and further show that vinpocetine’s activity is maintained during repeated administration.