title: Differing stereospecificities distinguish opiate receptor subtypes.
abstract: Paired stereoisomers of compounds active at the proposed mu, kappa and sigma classes of opiate receptors display differing stereoselectivity patterns at the receptor subtypes. The (-) isomers of cyclazocine and SKF-10047 are far more potent than the (+) isomers as displacers of [3H]dihydromorphine from receptors. However, the (-) isomers are only moderately more potent than the (+) isomers at displacing [3H]ethylketocyclazocine from kappa receptors in an assay controlled for radioligand binding to mu receptors, and the (+) and (-) isomers are similar in potency for displacement of [3H]phencyclidine (PCP) from sigma receptors. At the sigma/PCP receptor, (+) ketamine proved four times as potent as (-) ketamine, while the dioxalan derivative dexoxadrol is far more potent than its nearly inactive enantiomer levoxadrol. The results for the sigma/PCP receptor are in agreement with those of behavioral studies. Stereospecificity patterns may provide support for the concept of the opiate receptor subclasses as biochemically distinct entities.
mesh_terms: D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001665:Binding Sites; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000032:analysis; D011957:Receptors, Opioid / Q000032:analysis*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism
chemical_list: D001575:Benzomorphans; D011955:Receptors, Drug; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017478:Receptors, Phencyclidine