Sigma receptors mediated the psychotomimetic effects of N-allylnormetazocine (SKF-10,047), but not its opioid agonistic-antagonistic properties.
N Khazan, G A Young, E E El-Fakany, O Hong, D Calligaro
Neuropharmacology August 1, 1984 DOI: 10.1016/0028-3908(84)90015-7 via PubMed
Summary
AI-generated from the abstractThe prototype sigma agonist SKF-10,047 has opioid properties in its (-) isomer and psychotogenic properties in both its (+) and (-) isomers, similar to PCP. (-)-SKF-10,047 blocked EEG and behavioral effects of morphine in naive rats, precipitated withdrawal in morphine-dependent rats, produced physical dependence shown by naloxone-induced withdrawal, and displaced [3H]dihydromorphine from brain homogenates. (+)-SKF-10,047 did not produce dependence or displace [3H]dihydromorphine. This dissociation suggests sigma receptors are linked to psychogenic effects, not opioid effects, which are likely mediated by mu or kappa receptors.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | SKF-10 047 (-)-SKF-10 (+)-SKF-10 morphine naloxone |
| Key finding | The sigma agonist SKF-10,047 shows a dissociation: its (-) isomer has opioid activity, while both isomers have psychotogenic properties, suggesting sigma receptors mediate psychogenic rather than opioid effects. |
Abstract
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.