Beneficial Effect of Idebenone (CV-2619) on Cerebral Ischemia-Induced Amnesia in Rats

Abstract

An experimental model of amnesia induced by cerebral ischemia after one-trial passive avoidance learning was established to test the effects of a novel compound, 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-261 9), and some commonly used drugs in rats. One day after the vertebral artery was electrocauterized bilaterally, the common carotid artery was transiently occluded bilaterally to produce cerebral ischemia. The amnesia was estimated by the response latency for a rat to step from a light safety compartment to a dark compartment in which a foot-shock was given. The results of the retention test given 24 hr after the ischemia indicated that amnesia was successfully produced when the 200-600 sec ischemia was provided within 20 min after the avoidance learning. The effects of drugs on the amnesia induced by a 200-sec ischemia immediately after the avoidance learning were as follows: CV-2619 (10, 30 mg/kg, i.p. or p.o.) given before the retention test significantly increased the response latency, indicating a reversal effect on the amnesia. Physostigmine (0.1, 0.2 mg/kg, i.p.) and arginine-vasopressin (10 μg/kg, s.c.) were also effective, and calcium hopantenate (500 mg/kg, p.o.) showed a slight reversal action. Furthermore, CV-2619 (10 mg/kg, i.p.), given before or after the ischemia, significantly inhibited the appearance of amnesia. These findings suggest that CV-2619 exerts an ameliorating effect on memory disturbance induced by cerebral ischemia in rats.