Neurochemical investigation on the effects of a new diphenylpiperazine calcium antagonist, KB-2796, on the central dopaminergic system of rats
The results of KB-2796, a brand new diphenylpiperazine calcium antagonist, around the striatal dopaminergic system of rats were investigated in comparison to various calcium antagonists and also the dopamine antagonist chlorpromazine. The inhibiting aftereffect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was less strong than individuals of chlorpromazine and yet another diphenylpiperazine analogues, flunarizine and cinnarizine, and much more potent than individuals of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) didn’t have impact on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes acquired in the rat at 36 hr and seven days after repeated administration for 18 days, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) elevated Bmax values by 47% and 31%, correspondingly, at 36 hr, although not at seven days following the final administration. At 1 hr following the single administration, KB-2796 (30, 100 mg/kg, p.o.) didn’t have impact on the information of dopamine and it is metabolites within the striatum, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) elevated the amount of homovanillic acidity. These results indicate that flunarizine may affect dopaminergic neurotransmission by partly blocking dopamine D2 receptors, while KB-2796 has minimal in Lomerizine vivo impact on the dopaminergic system.