NEUROENDOCRINE RESPONSES PRODUCED BY ENANTIOMERIC PAIRS OF DRUGS THATINTERACT WITH PHENCYCLIDINE AND SIGMA-RECEPTORS

The present study characterized the response of the hypothalamo-pituit ary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats we re injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpip eridine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadr ol and levoxadrol) or pentazocine, and plasma levels of adrenocorticot ropin (ACTH) and corticosterone were determined by radioimmunoassay. T he effects of the enantiomers of PCMP and dioxadrol showed stereospeci ficity 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 a ffinity for binding to PCP receptors, the potency of the enantiomers o f pentazocine did not. These results suggest that although the stimula tion of the hypothalamo-pituitary-adrenal axis by PCP and drugs with P CP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.