The interactions of 1-alkyl-4,4-diphenylpiperidines with opiate receptors

1-Alkyl-4,4-diphenylpiperidines inhibit the binding of mu- and delta-opiate receptor agonists to crude synaptosomal membranes of rat brain. Opiate receptor affinity is dependent on the nature of the 1-alkyl substitution. In displacing [3H]etorphine, [3H]dihydromorphine and [3H][D-Ala2,D-Leu5] enkephalin, the 1-methyl-derivative was most effective (IC50 [3H]etorphine = 9 microM, IC50 [3H]dihydromorphine = 0.71 microM, IC50 [3H][D-Ala2,D-Leu5]enkephalin = 2.1 microM). 1-t-Butyl-4,4-diphenylpiperidine and its 1-isopropyl analogue, used as antiparkinsonism drugs, exhibit distinctly lower inhibiting concentration values (50% inhibition, IC50 values).