PHARMACOLOGICAL EVALUATION OF N-ALLYNORMETAZOCINE (SKF-10,047) ON THE BASIS OF ITS DISCRIMINATIVE STIMULUS PROPERTIES IN THE RAT

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (1) , 144-152
Abstract
The pharmacological properties of the discriminative stimulus effects of the prototypic .sigma. receptor agonist N-allylnormetazocine (NANM, SKF 10,047) were evaluated. Rats were trained to discriminate between saline and 3.0 or 5.6 mg/kg of NANM in a 2-choice, shock-avoidance procedure. NANM-like stimulus control of behavior was produced by the opiates, in order of relative molar potency, cyclazocine > NANM > N-propyinormetazocine hydrochloride > levallorphan > dextrorphan > pentazocine. Metazocine produced NANM-like discriminative effects but only when tested concomitantly with naloxone. Seven other opiate derivatives, including levorphanol, ethylketazocine and nalorphine, failed to produce NANM-like discriminative stimuli. Among enantiomeric pairs tested in the lower training dose group, d-NANM and l-NANM as well as levallorphan and dextrallorphan were equipotent, but the levo isomers of cyclazocine and pentazocine were more potent than their dextro counterparts; dextrorphan but not levorphanol produced NANM-like discriminative stimuli. In the lower training dose group, the opioid antagonist naloxone failed to antagonize the NANM-like discriminative effects of NANM, l-cyclazocine and levallorphan, although naloxone did produce a parallel shift to the right of the dose-effect curve for pentazocine, and unmasked NANM-like effects of higher doses of metazocine. The nonopiate psychoactive drugs phencyclidine [PCP] and dexoxadrol, but not its enantiomer levoxadrol, produced NANM-like discriminative stimuli. Propranolol also occasioned an appreciable percentage of NANM-appropriate responding in the lower training dose group but not the higher dose group. Diazepam, d-amophetamine, d-lysergic acid diethylamide tartrate, imipramine, clonidine and haloperidol also failed to produce NANM-like discriminative stimuli in the lower training dose group. Evidently, the discriminative stimuli properties of NANM are distinguishable from those of morphine and ethylketazocine but similar to those of dissociative anesthetics such as PCP. Additional support to the hypothesis that .sigma. receptors mediate the common actions of NANM and PCP was indicated.