COMPARATIVE STUDIES ON THE AFFINITIES OF K-Ⅱ AND U-50488H FOR KAPPA OPIATE RECEPTOR

3, 4-Dichloro-N-methyl-N-trans-2-(1-Δ³-pyrrolinyi)-cyclohexyl benzenacetamide hydrochloride (K-Ⅱ) is a novel analogue of U-50488H. Previous studies have demonstrated that K-Ⅱ is more potent than U-50488H in analgesic activity in mice and in inhibitory effect on electrically induced contractions of the isolated rabbit vas deferens. In this paper, we determined the affinities of K-Ⅱ and U-50488H for kappa opiate receptor in guinea pig cerebellum and frontal cortex using radioreceptor binding assay (saturation studies and competition studies), and calculated Ki values of K-Ⅱ and U-50488H by the Cheng-Prusoff equation. The results indicate that the affinity of K-Ⅱ for kappa opiate receptor is 6～42 times greater than that of U-50488H. The selectivity of K-Ⅱ for opiate receptor subtypes is being studied.