Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.
Typical antipsychotics such as haloperidol exert their therapeutic effects via blockade of dopamine (DA) D(2) receptors, leading to extrapyramidal symptoms (EPS) in humans and catalepsy in rodents. In contrast, atypical antipsychotics and new generation D(2)/5-HT(1A) antipsychotics have low cataleptogenic potential. However, there has been no systematic comparative study on the effects of these different classes of antipsychotics in non-human primates, a species displaying a more sophisticated repertoire of behavioural/motor activity than rats. Once weekly, six young adult female non-haloperidol-sensitised cynomolgus monkeys were treated i.m. with a test compound and videotaped to score catalepsy-associated behaviour (CAB: static postures, unusual positions and crouching). Haloperidol, risperidone, olanzapine, nemonapride and remoxipride induced, to different extents, an increase in unusual positions (a response akin to dystonia), some crouching and static postures. In contrast, clozapine, quetiapine, ziprasidone and aripiprazole produced much lower or no unusual positions; clozapine also produced marked increases in static postures and crouching. Among novel D(2)/5-HT(1A) antipsychotics, SLV313 and F15063 augmented the number of unusual positions, albeit at doses 16-63 times higher than those of haloperidol for approximately the same score. SSR181507 and bifeprunox produced moderate static postures, little crouching and negligible unusual positions. These data provide the first comparative analysis in cynomolgus monkeys of EPS liability of conventional, atypical and novel D(2)/5-HT(1A) antipsychotics. They indicate that the latter are less prone than haloperidol to produce CAB, and provide a basis for comparison with rodent catalepsy studies.
Auclair
Agnès L
AL
Division of Neurobiology 2, Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres, France.
Kleven
Mark S
MS
Barret-Grévoz
Catherine
C
Barreto
Martine
M
Newman-Tancredi
Adrian
A
Depoortère
Ronan
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000009:adverse effects; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D000068180:Aripiprazole; D001549:Benzamides / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects; D001583:Benzoxazoles / Q000009:adverse effects; D002375:Catalepsy / Q000139:chemically induced*; D003024:Clozapine / Q000009:adverse effects; D003987:Dibenzothiazepines / Q000009:adverse effects; D004146:Dioxanes / Q000009:adverse effects; D018492:Dopamine Antagonists / Q000009:adverse effects*; D005260:Female; D006220:Haloperidol / Q000009:adverse effects; D008252:Macaca fascicularis; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000009:adverse effects; D017330:Remoxipride / Q000009:adverse effects; D018967:Risperidone / Q000009:adverse effects; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects; D014326:Tropanes / Q000009:adverse effects; D014741:Video Recording
C480819:(3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine monohydrochloride; C504317:1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-((5-(4-fluorophenyl)-3-pyridinyl)methyl)piperazine; D014150:Antipsychotic Agents; D001549:Benzamides; D001583:Benzoxazoles; D003987:Dibenzothiazepines; D004146:Dioxanes; D018492:Dopamine Antagonists; D010879:Piperazines; D015363:Quinolones; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D014326:Tropanes; D017330:Remoxipride; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000068180:Aripiprazole; C509981:bifeprunox; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine; C030265:nemonapride