cinnarizine and Dyskinesia--Drug-Induced

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.

Topics: Amphetamine; Animals; Antipsychotic Agents; Calcium Channel Blockers; Catalepsy; Central Nervous System Stimulants; Cinnarizine; Dizocilpine Maleate; Dyskinesia, Drug-Induced; Excitatory Amino Acid Antagonists; Haloperidol; Hyperkinesis; Male; Mice; Motor Activity; Psychotic Disorders

A retrospective study was carried out to investigate the evolution of patients diagnosed with cinnarizine-induced parkinsonism (CIP) over the past 15 years. A total of 74 cases of CIP were found among 172 patients with drug-induced parkinsonism (DIP). Both CIP and other DIP were significantly more frequent in women. No clinical differences between CIP and other DIP were found. Most of the patients (66 of 74) completely recovered after cinnarizine withdrawal in 1-16 months. Eleven patients later developed Parkinson's disease; four of them had previously recovered. Five patients had tardive dyskinesia. CIP accounts for a high proportion of DIP referred to neurologists in populations in which cinnarizine is widely prescribed. The symptoms typically resolve after drug withdrawal, although complete recovery may take more than 1 year.

Topics: Aged; Cinnarizine; Dizziness; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Neurologic Examination; Parkinson Disease, Secondary; Retrospective Studies; Spain; Substance Withdrawal Syndrome; Vertebrobasilar Insufficiency

Over the last few years, cases of movement disorders induced by flunarizine and cinnarizine have been increasingly reported. We describe a series of 101 patients, whose ages ranged from 37 to 84 years (mean 69.1), developing abnormal movements frequently associated with depression, secondary to treatment with either or both drugs. Symptoms closely resembled those induced by neuroleptic drugs and remitted on drug discontinuance in all but five cases after 5-22 months' follow-up. Whether or not such undesirable side effects are attributable to calcium antagonism and/or dopamine receptor blockade, long-term treatment with flunarizine or cinnarizine should be discouraged, particularly in the elderly.

Topics: Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Cinnarizine; Depression; Dyskinesia, Drug-Induced; Dystonia; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Tremor

12 subjects, 8 women and 4 men, presented with extrapyramidal motor signs and psychic depression after treatment with flunarizine for between 3 weeks and 15 months. One woman presented with severe symptoms and 20 months after stopping flunarizine she still had dyskinesia and akathisia. The other patients showed partial or complete improvement after withdrawal of the drug.

Topics: Aged; Akathisia, Drug-Induced; Cinnarizine; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Psychoses, Substance-Induced