Reversal of haloperidol-induced extrapyramidal side effects in cebus monkeys by 8-hydroxy-2-(di-n-propylamino)tetralin and its enantiomers.
(+/-)-8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), (+)-8-OH-DPAT, and (-)-8-OH-DPAT produced dose-related reversals of haloperidol-induced extrapyramidal side effects (EPS) in cebus monkeys, with all compounds producing similar almost complete reversals at 0.1 mg/kg i.m. These compounds were more potent than apomorphine, which reversed haloperidol-induced EPS at 0.3, but not 0.1, mg/kg i.m. The data indicate that the reversal of haloperidol-induced EPS by (+/-)-8-OH-DPAT and its enantiomers is mediated via effects at 5-HT1A receptors, not dopamine D2 receptors. Thus, inclusion of 5-HT1A agonist activity in novel antipsychotics may reduce EPS liability.
Christoffersen
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Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, Michigan 48105, USA.
Meltzer
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LT
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001058:Apomorphine / Q000494:pharmacology; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000188:drug therapy*; D002428:Cebus; D005260:Female; D006220:Haloperidol / Q000009:adverse effects*; D008297:Male; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors
D018726:Anti-Dyskinesia Agents; D014150:Antipsychotic Agents; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D001058:Apomorphine