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 (0.25 mg/kg) and amphetamine (5mg/kg) locomotor effects at doses as low as 20mg/kg, having no incremental effect at 60 or 180 mg/kg. Regarding side-effects, cinnarizine induced no catalepsy in mice at the effective dose of 20 mg/kg, inducing only mild catalepsy at the doses of 60 and 180 mg/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.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Oscar P
OP
Dall'Igna
Adriano B L
AB
Tort
Diogo O
DO
Souza
Diogo R
DR
Lara
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002936:Cinnarizine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000523:psychology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology
D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D002936:Cinnarizine; D016291:Dizocilpine Maleate; D000661:Amphetamine; D006220:Haloperidol