Reversal of Haloperidol-Induced Extrapyramidal Side Effects in Cebus Monkeys by 8-Hydroxy-2-(di-n-propylamino)tetralin and Its Enantiomers


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Brief Report


Neuropsychopharmacology (1998) 18 399-402.10.1038/sj.npp.1395157 Reversal of Haloperidol-Induced Extrapyramidal Side Effects in Cebus Monkeys by 8-Hydroxy-2-(di-n-propylamino)tetralin and Its Enantiomers Curt L Christoffersen BA and Leonard T Meltzer Ph.D



Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, Michigan USA Correspondence: Dr Leonard T Meltzer, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., 2800 Plymouth Road, Ann Arbor, MI 48105



ABSTRACT

(±)-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 IM. These compounds were more potent than apomorphine, which reversed haloperidol-induced EPS at 0.3, but not 0.1, mg/kg IM. The data indicate that the reversal of haloperidol-induced EPS by (±)-8-OH-DPAT and its enantiomers is mediated via effects at 5-HT_1A receptors, not dopamine D₂ receptors. Thus, inclusion of 5-HT_1A agonist activity in novel antipsychotics may reduce EPS liability. Keywords: Extrapyramidal side effects; Serotonin-_1A; Haloperidol; Cebus monkeys; Dopamine antagonists; Dystonias

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