Calcium Antagonists, Neuroleptics and Brain Dopamine

Abstract

Aside from the blockade induced by calcium channel antagonist (CCA) drugs on excitable tissue, there appears to be a role for CCA in dopamine (DA) function as demonstrated by verapamil (VER) inhibition of DA release from the arcuate nucleus (DiRenzo et al.,1984), their benefit in the treatment of movement disorders (Goldstein, 1984), the direct competition with DA for D2 receptor binding in the striatum (DeVries and Beart, 1985), and their apparent therapeutic benefit in mania (Giannini et al., 1984) and schizophrenia (Giannini and Loiselle, 1985). Moreover, certain neuroleptics which block DA receptors also act as CCA (Gould et al, 1983). These DA blocking drugs include the diphenylbutylpiperidines (eg., pimozide, penfluridol, etc), which are structurally similar to VER, Thioridazine and clozapine also possess relatively potent CCA activities. The occurrence of less extrapyramidal side-effects, with these neuroleptics compared to neuroleptics without significant CCA properties argues for the possible benefits of concomitant blockade of calcium channels and DA D2 receptors in the prophylaxis and treatment of tardive dyskinesia. The following studies were directed at in vivo effects of CCA on brain DA function.