Sigma receptors mediated the psychotomimetic effects of N-allylnormetazocine (SKF-10,047), but not its opioid agonistic-antagonistic properties.
Our present findings suggest that SKF-10,047, the prototype sigma agonist, has its opioid entity residing with its (-) isomer, while both its (+) and (-) isomers possess psychotogenic properties similar to those produced by PCP. We found that (-)-SKF-10,047 blocks EEG and behavioral effects of morphine in the naive rat, precipitates withdrawal in morphine-dependent rats, produces physical dependence as evidenced by naloxone-induced withdrawal, and displaces [3H]dihydromorphine from brain homogenates. (+)-SKF-10,047 did not produce dependence upon chronic treatment, and it did not displace [3H]dihydromorphine from brain homogenates. Such pharmacodynamic dissociation with SKF-10,047 suggests an association of sigma receptors with psychogenic, but not opioid effects. The latter are most likely mediated by mu or kappa receptors.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D006213:Hallucinogens; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology*; D017480:Receptors, sigma; D013237:Stereoisomerism
D006213:Hallucinogens; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; D009020:Morphine; D004090:Dihydromorphine; D010620:Phenazocine