Neuroendocrine responses produced by enantiomeric pairs of drugs that interact with phencyclidine and sigma receptors.
The present study characterized the response of the hypothalamo-pituitary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)-pentazocine produced greater responses than (+)-pentazocine, the two enantiomers of SKF 10,047 did not show stereoselectivity. Although the potency of the enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP receptors, the potency of the enantiomers of pentazocine did not. These results suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis by PCP and drugs with PCP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.
Pechnick
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RN
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70119-2799.
Poland
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RE
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004148:Dioxolanes / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013566:Sympathomimetics / Q000378:metabolism / Q000494:pharmacology
D000700:Analgesics; D004148:Dioxolanes; D010880:Piperidines; D017480:Receptors, sigma; D013566:Sympathomimetics; C036590:1-(1-phenylcyclohexyl)-3-methylpiperidine; C005840:dioxadrol; C012134:SK&F 10047; C579649:levoxadrol; D000324:Adrenocorticotropic Hormone; D010620:Phenazocine; D010622:Phencyclidine; C579650:dexoxadrol; D003345:Corticosterone