SCH 23390 dissociated from conventional neuroleptics in apomorphine climbing and primate acute dyskinesia models |
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Authors: | S Gerhardt R Gerber J M Liebman |
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Institution: | Neuroscience Research Subdivision, CIBA-GEIGY Pharmaceuticals, Summit, NJ 07901, USA |
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Abstract: | SCH 23390 induced only a negligible incidence of the acute dyskinetic syndrome, a predictor of neuroleptic-induced extrapyramidal liability, in squirrel monkeys. However, haloperidol-induced dyskinesias were potentiated by SCH 23390 and were blocked by the D-1 agonist, SKF 38393. When administered orally or intraperitoneally to mice, SCH 23390 showed a considerably wider dose separation than did conventional neuroleptics between antagonism of apomorphine climbing and antagonism of stereotyped sniffing. Clinically relevant distinctions may exist between D-1 and D-2 antagonists, with D-1 antagonists (exemplified by SCH 23390) showing lower, although possibly not negligible, potential to cause extrapyramidal side effects. |
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