The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia.
To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.
Fukuoka
T
T
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Nakano
M
M
Kohda
A
A
Okuno
Y
Y
Matsuo
M
M
D000208:Acute Disease; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000633:toxicity*; D002144:Callithrix; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D004421:Dystonia / Q000139:chemically induced* / Q000523:psychology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D006220:Haloperidol