EFFECTS OF CALCIUM-ANTAGONISTS ON THE DOPAMINE SYSTEM

Calcium channel antagonists are drugs currently used in the treatment of neurological and cardiovascular disorders and occasionally produce parkinsonism and movement disorders as a side effect. We investigated the effects of calcium channel antagonists on the pharmacology of dopa mine systems in vivo and in vitro. Flunarizine, cinnarizine, and dilti azem reduce the viability of dopamine-rich human neuroblastoma cells i n vitro. These compounds plus verapamil, nifedipine, and nicardipine r educe H-3-spiperone binding to bovine striatal membranes, H-3-dopamine uptake, K+-induced H-3-dopamine release, and apomorphine-induced rota tion, but not amphetamine-induced rotation, in 6-OH-dopamine-lesioned rats. Therefore, all calcium channel antagonists tested reduce dopamin e neurotransmission in vitro and in vivo, whereas the evidence of toxi city for dopamine cells in vitro is restricted to flunarizine, cinnari zine, and diltiazem. The clinical relevance of these toxic effects may depend on several factors, including age, penetration across the bloo d-brain barrier, and types of calcium channels present in the differen t neuronal subtypes. On the other hand, the finding of dopamine-regula ting properties not associated to neurotoxic effects in the dihydropyr idines and verapamil provides new putative therapeutic tools for the t reatment of neurologic disorders associated with dopamine hyperactivit y.