Stereoisomers of [3H]-N-allylnormetazocine bind to different sites in mouse brain.

(+)- and (-)-[3H]-N-allylnormetazocine (NANM) were synthesized and evaluated for binding to mouse brain membranes. Scatchard analysis of the saturable binding of (-)-[3H]NANM suggested a single class of binding sites with an apparent KD of 2.1 nM and an estimated maximum binding of 197 fmol/mg of protein. Increasing the concentration of Na+, K+, Mn++ or Ca++ decreased (-)-[3H]NANM specific binding. (-)-[3H]NANM apparently binds to the mu opiate receptor in that (-)-isomers, but not the (+)-isomers, of N-cis-3-chloroallylnormetazocine, N-propynylnormetazocine, pentazocine, cyclazocine, naloxone, phenazocine and morphine competed for binding. (-)-Isomers of ethylketocyclazocine, ketocyclazocine and NIH 9101 also displaced (-)-[3H]NANM binding which suggested kappa activity in addition to mu activity. Phencyclidine and its analogs did not bind to the (-)-[3H]NANM site. Scatchard analysis of saturable binding of (+)-[3H]NANM also revealed a homogeneous population of binding sites with apparent KD of 12 nM and an estimated maximum binding of 360 fmol/mg of protein. This binding site was unaffected by increasing concentrations of Na+ and K+, but binding was decreased by high concentrations of Mn++ and Ca++. The (+)-isomers of the benzomorphans N-cis-3-chloroallylnormetazocine, phenazocine, pentazocine and cyclazocine effectively displaced (+)-[3H]NANM binding. In addition, the (+)-isomers of ketocyclazocine and ethylketocyclazocine, as well as dextrorphan, a (+)-morphinan, bind to the (+)-[3H]NANM site. The (-)-isomers of mu agonist/antagonists and kappa agonists competed poorly, or not at all, for the (+)-[3H]NANM site whereas phencyclidine and related compounds exhibited a low affinity for this site.(ABSTRACT TRUNCATED AT 250 WORDS)