Chronic olanzapine or sertindole treatment results in reduced oral chewing movements in rats compared to haloperidol.
Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report results of the association of oral chewing movements in rats with chronic administration of two new antipsychotic drugs, olanzapine and sertindole. Because each of these antipsychotic drugs has a very low incidence of acute Parkinsonism in human studies, they are candidates for showing a low tardive dyskinesia risk. Neither new drug produced a significant incidence of haloperidol-like chewing in rats, nor did movement ratings after their chronic administration differ from placebo; whereas, haloperidol produced a 60% prevalence of purposeless chewing and a prevalence significantly increased from placebo. This low rate of oral dyskinesias in rats is consistent with several of the preclinical characteristics of the drugs and correlates with their low acute motor side effects in clinical trials. We propose, although have not yet tested in humans, that these animal results will predict low TD liability of these drugs.
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.
X M
XM
Gao
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K
Sakai
C A
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Tamminga
D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000633:toxicity*; D001569:Benzodiazepines; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D006220:Haloperidol / Q000097:blood / Q000633:toxicity*; D007093:Imidazoles / Q000097:blood / Q000633:toxicity*; D007211:Indoles / Q000097:blood / Q000633:toxicity*; D008297:Male; D008409:Mastication; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D010890:Pirenzepine; C066304:sertindole; D006220:Haloperidol; D000077152:Olanzapine