Pharmacological evaluation of N-allynormetazocine (SKF 10,047) on the basis of its discriminative stimulus properties in the rat.
The purpose of the present experiments was to evaluate the pharmacological properties of the discriminative stimulus effects of the prototypic sigma receptor agonist N-allylnormetazocine (NANM, SKF 10,047). Rats were trained to discriminate between saline and 3.0 or 5.6 mg/kg of NANM in a two-choice, shock-avoidance procedure. NANM-like stimulus control of behavior was produced by the opiates, in order of relative molar potency, cyclazocine greater than NANM greater than N-propylnormetazocine HCI greater than levallorphan greater than dextrorphan greater than 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, whereas 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 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-amphetamine, d-lysergic acid diethylamide tartrate, imipramine, clonidine and haloperidol also failed to produce NANM-like discriminative stimuli in the lower training dose group. The present results demonstrate that the discriminative stimulus properties of NANM are distinguishable from those of morphine and ethylketazocine but similar to those of dissociative anesthetics such as phencyclidine and lend additional support to the hypothesis that sigma receptors mediate the common actions of NANM and phencyclidine.
D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism
D001575:Benzomorphans; D009270:Naloxone; C012134:SK&F 10047; D011433:Propranolol; D010620:Phenazocine; D010622:Phencyclidine