A COMPARISON OF (-)-DEOXYBENZOMORPHANS DEVOID OF OPIATE ACTIVITY WITHTHEIR DEXTROROTATORY PHENOLIC COUNTERPARTS SUGGESTS ROLE OF SIGMA(2) RECEPTORS IN MOTOR FUNCTION (VOL 231, PG 61, 1993)

Three novel benzomorphans, (+)-N-benzylnormetazocine, (-)-deoxy-N-benz ylnormetazocine, and (-)-deoxypentazocine were tested for their abilit y to produce circling behavior in rats following intranigral microinje ctions. Dose studies revealed the following rank order of potency: (-) -deoxypentazocine > (-)-deoxy-N-benzylnormetazocine > (+)-N-benzylnorm etazocine. This rank order approximates that for affinities for sigma2 receptors but not sigma1 receptors. It is very unlikely that the effe cts of the (-)-deoxybenzomorphans were mediated by opiate receptors fo r the following reasons: (1) consistent with the known requirement for the phenolic hydroxyl group for opiate activity, both (-)-deoxy compo unds showed very low affinity for opiate receptors; (2) naloxone (4 mu g) co-administered with (-)-deoxy-N-benzylnormetazocine failed to redu ce its efficacy; (3) both (-)-deoxy compounds failed to produce marked analgesic effects in the tail flick test following systemic injection s of 20 mg/kg s.c. These findings suggest that sigma2 receptors mediat e the motor effects of sigma ligands in rats.