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The simultaneous addition of [D-Ala2, D-Leu5]-enkephalin and morphiceptin at concentrations at which 98% of enkephalin (delta) and morphine (mu) receptors are occupied only partially inhibits the binding of [3H]diprenorphine to rat brain membranes. These conditions, furthermore, do not affect the curves for displacement of [3H]diprenorphine binding by unlabeled diprenorphine. These data suggest that [3H]diprenorphine binds to a third subtype of opiate binding site, which has high affinity for diprenorphine but very low affinity for mu and delta agonists. The [3H]-diprenorphine binding observed in the presence of morphiceptin and [D-Ala2, D-Leu5]enkephalin exhibits high affinity for several benzomorphan drugs in the chemical family of 6,7-benzomorphan (e.g., cyclazocine, ethylketocyclazocine, SKF 10047, UM 1072, oxilorphan, etc). Because of its selectivity for most benzomorphan drugs, this putative receptor site is tentatively referred to as a benzomorphan binding site. Its regional distribution in rat brain is similar to that of morphine (mu) receptors but differs from that for enkephalin (delta) receptors. The content of benzomorphan binding sites in rat brain is only one-half to one-third that of morphine receptors. The relative affinities of various opioids to morphine enkephalin, and benzomorphan binding sites are also described.

Novel opiate binding sites selective for benzomorphan drugs.