A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function.

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.