Clinical neuropharmacology of calcium antagonists

Experimental and clinical data clearly demonstrate that calcium antagonists (CA) may have an action on the central nervous system (CNS). The cerebrovascular action of CA justifies their use in cerebral ischaemia, vasospasm and hypoxia. Several clinical trials have demonstrated such beneficial effects. On the other hand a number of reports indicate that CA may have a direct neuronal effect, although most of such trials have not been verified or are mere case reports. In addition, the large number of conditions susceptible to being corrected by CA is impressive: epilepsy, pain, dystonia, dyskinesia, psychiatric conditions, etc. Other papers are disconcerting that report extrapyramidal disorders induced by flunarizine and cinnarizine in the elderly, whereas nicardipine does not produce such side effects and may even alleviate some parkinsonian symptoms. In various experimental models (e.g. stroke, oedema), pharmacological effects have been shown to vary from one compound to the other. Two main questions are yet to be answered: 1) has the direct neuronal effect of CA been clearly established? 2) are the multiple clinical effects on the CNS really linked to calcium antagonism?