Cinnarizine has an atypical antipsychotic profile in animal models of psychosis

Cinnarizine, a drug known as a calcium channel blocker, is currently used for the treatment of migraine and vertigo. Induction of extrapyramidal signs by cinnarizine has been reported in the elderly, which is related to its moderate antagonistic properties at dopamine D2 receptors, resembling the mechanism of action of most antipsychotic drugs. Despite this effect, cinnarizine has never been tested as a putative antipsychotic drug. Here we evaluate the potential effect of cinnarizine in two pharmacological models of psychosis, namely amphetamine- and MK-801-induced hyperlocomotion, as well as its ability to induce catalepsy. Cinnarizine significantly counteracted MK-801 (0.25mg/kg) and amphetamine (5mg/kg) locomotor effects at doses as low as 20mg/kg, having no incremental effect at 60 or 180mg/kg. Regarding side-effects, cinnarizine induced no catalepsy in mice at the effective dose of 20mg/kg, inducing only mild catalepsy at the doses of 60 and 180mg/kg. Based on these results and on the antagonist effect of cinnarizine on dopamine D2 receptors, we suggest that it has a potential antipsychotic effect with an atypical profile that should be evaluated clinically.