Demonstration of non-opioid sigma binding with (d)3H-SKF 10047 in guinea pig brain.

A non-opioid binding site to (d)3H-SKF 10047 (N-allyl-normetazocine), the prototypic ligand for the sigma or PCP-like receptor, was demonstrated. The (d) isomer of 3H-SKF 10047 was used to demonstrate a stereospecific low affinity binding site with a Kd of 173nM. It was naloxone insensitive with an IC50 of greater than 10,000nM, which defined it as non-opioid. Traditional mu compounds like morphine and FK 33824 were also inactive, with IC50's of greater than 10,000nM. Kappa compounds such as ethylketocyclazocine and U-50,488H were active as were all of the benzmorphans tested, with butorphanol the least active. The known antipsychotic haloperidol was the most active compound tested, with an IC50 of 11nM. Other antipsychotics which demonstrated activity were chlorpromazine and pimozide. The atypical antipsychotic clozapine was inactive.