Author: Walker-J-M. Bowen-W-D. Patrick-S-L. Williams-W-E. Mascarella-S-W. Bai-X. Carroll-F-I.

Title: A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function [published erratum appears in Eur J Pharmacol 1993 Jun 4;236(3):495]

Source: Eur-J-Pharmacol. 1993 Jan 26. 231(1). P 61-8.

Journal Title: EUROPEAN JOURNAL OF PHARMACOLOGY.

Abstract: Three novel benzomorphans, (+)-N-benzylnormetazocine, (-)- deoxy-N-benzylnormetazocine, and (-)-deoxypentazocine were tested for their ability to produce circling behavior in rats following intranigral microinjections. Dose studies revealed the following rank order of potency: (-)-deoxypentazocine > (- )-deoxy-N-benzylnormetazocine > (+)-N-benzylnormetazocine. This rank order approximates that for affinities for sigma 2 receptors but not sigma 1 receptors. It is very unlikely that the effects of the (-)-deoxybenzomorphans were mediated by opiate receptors for the following reasons: (1) consistent with the known requirement for the phenolic hydroxyl group for opiate activity, both (-)-deoxy compounds showed very low affinity for opiate receptors; (2) naloxone (4 micrograms) co- administered with (-)-deoxy-N-benzylnormetazocine failed to reduce its efficacy; (3) both (-)-deoxy compounds failed to produce marked analgesic effects in the tail flick test following systemic injections of 20 mg/kg s.c. These finding suggest that sigma 2 receptors mediate the motor effects of sigma ligands in rats.