Ameliorating effect of clentiazem (TA-3090), a new Ca antagonist, on the impaired learning ability of poststroke SHRSP

Abstract

We investigated the influence of clentiazem (8-chloro-diltiazem, (+)(2S,3S)-3-acetoxy-8-chloro-5-[2-(dimethyl-amino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one maleate, TA-3090) and other Ca antagonists on the impaired learning ability in poststroke spontaneous hypertensive rats stroke prone (SHRSP) using a shuttle box. SHRSP were given 1% NaCl solution as drinking water until the development of stroke (poststroke SHRSP). Active avoidance task was started from the fourth day after the onset of stroke. Over a period of 20 sessions (15 trials/session/day), the mean avoidance rate of the poststroke SHRSP was significantly lower than that of the nonstroke control group that was not given the salt solution. Clentiazem (1, 3, and 10 mg/kg/day) administered orally for 23 days after the development of stroke increased the avoidance rate in a dose-dependent manner. Nimodipine (1 and 10 mg/kg/day) also increased the avoidance rate, but its effect was not dose dependent. We also investigated the influence of clentiazem and other Ca antagonists on the passive avoidance performance by mice using a light-dark box. Clentiazem (3, 10, and 30 mg/kg) and other Ca antagonists, nimodipine (1 mg/kg) and nicardipine (10 mg/kg), all failed to protect either CO 2- or electroconvulsive shock (ECS)-induced avoidance deficit when administered orally 1 h before the acquisition or retention trial. These results may be explained by the possibility that the Ca antagonists may ameliorate the impaired learning ability in poststroke SHRSP through their improving effect on the cerebral circulation disturbance.