(+)-and (-)-Phenazocine enantiomers: Evaluation of their dual opioid agonist/?₁ antagonist properties and antinociceptive effects

cis-N-Substituted N-normetazocine enantiomers possess peculiar pharmacological profiles. Indeed, dextro enantiomers bind with high affinity cri receptor while opposite enantiomers bind opioid receptors. In spite of their stereochemistry, cis-N-2-phenylethyl N-normetazocine (phenazocine) enantiomers showed mixed opioid/sigma(1) receptor profiles and a significant in vivo analgesia. To the best of our knowledge, there is no information available regarding the evaluation of sigma(1) pharmacological profile in the antinociceptive effects of (+)- and (-)-phenazocine. Therefore, the present study was designed to ascertain this component by in vitro and in vivo studies. In particular, we tested the cri affinity of both enantiomers by a predictive binding assay in absence or presence of phenytoin (DPH). Our results showed that DPH (1 mM) did not increase the sigma(1) receptor affinity of (+)-arid (-)-phenazocine (K-i=3.8 +/- 0.4 nM