-The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the striatal dopaminergic system of rats were investigated in comparison with var ious calcium antagonists and the dopamine antagonist chlorpromazine. The inhibiting effect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was weaker than those of chlorpromazine and the other diphenylpiperazine analogues, flunarizine and cinnarizine, and more potent than those of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) had no effect on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes obtained from the rat at 36 hr and 7 days after repeated administration for 18 days, whereas flu narizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased Bmax values by 47% and 31%, respectively, at 36 hr, but not at 7 days after the final administra tion. At 1 hr after the single administration, KB-2796 (30, 100 mg/kg, p.o.) had no effect on the content of dopamine and its metabolites in the striatum, whereas flunar izine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased the level of homovanillic acid. These results indicate that flunarizine may affect dopaminergic neurotransmission by partially blocking dopamine D2 receptors, while KB-2796 has negligible in vivo effect on the dopaminergic system.

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