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. (+)-SKP-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.
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