PECULIAR EFFECTS OF ISRADIPINE AND DARODIPINE ON THE RAT-BRAIN DOPAMINERGIC SYSTEM

1. Darodipine and isradipine are dihydropyridine calcium antagonists w hich easily cross the blood-brain barrier displaying high affinity and specificity for the brain ''L'' type voltage-sensitive calcium channe l. In rat striatum and fronto-parietal cortex the effects of i.p. admi nistration of these drugs on the dopaminergic system were evaluated. 2 . Both drugs showed neuroleptic-like activity on spontaneous motility at a dose of 5 mg/kg or more. 3. Isradipine, being almost ineffective in the frontoparietal cortex, affected the striatal DA turnover. On th e contrary, darodipine affected the DA turnover of the frontoparietal cortex, being almost ineffective in the striatum. 4. Both drugs, unlik e nimodipine, appeared to display their antidopaminergic effects by en hancing the intraneuronal DA metabolism. 5. It was concluded that the antidopaminergic properties of isradipine and darodipine are character ized by their regional specificity and a peculiar profile of actions. However, these drugs (as well as nimodipine and other calcium antagoni sts) show neuroleptic-like effects at doses which should markedly affe ct the cardiovascular system.