Memory effects of the Ca2+ and 5-HT antagonists dotarizine and flunarizine.

In experiments on Wistar and Long Evans rats, using behavioral methods for passive (step-down and step-through) and active (shuttle-box two-way avoidance with punishment reinforcement) the newly synthesized diphenyl-methyl-piperazine derivative with Ca2+ and 5-HT antagonistic action dotarizine (DOT) administered repeatedly at oral doses of 50 and 10 mg/kg in some cases improve memory process. Under the same experimental conditions the chemically related to dotarizine Ca2+ antagonist flunarizine significantly facilitated retention. In old (Long Evans and Wistar) rats DOT in large dose decreases values of learning criterion. Probably this is a manifestation of the inherent to drugs with nootropic action "therapeutic window". Earlier investigations of the same and other authors suggest the participation of serotonergic neurotransmission in the mechanism of the memory effects of the drug DOT.