Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-3H SKF 10,047 and 3Hhaloperidol binding in guinea pig brain membranes.

The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-3HSKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-3HSKF 10,047 bound to a single class of sites with a Kd of 4 X 10(-8) M and a Bmax of 333 fmol/mg of protein. This binding was different from mu, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-3HSKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol greater than perphenazine greater than fluphenazine greater than acetophenazine greater than trifluoperazine greater than molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-3HSKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-3HSKF 10,047 binding sites did not correlate with those for 3Hspiperone (dopamine D2) sites. 3H-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-SKF 10,047. In the striatum, about half of the saturable 3Hhaloperidol binding was to 3Hspiperone (D2) sites and the other half was to sites similar to (+)-3HSKF 10,047 binding sites.