U50,488: A kappa-selective agent with poor affinity for mu 1 opiate binding sites

Abstract

Although a number of potent kappa ligands have been reported, virtually all also label mu receptors with very high affinity. In contrast, we found that U50,488 is highly selective for kappa sites (K i 12 nM) when compared to both morphine-selective (mu 2) or delta receptors (both K i values > 500 nM) confirming earlier reports. However, these reports did not examine interactions with mu 1 receptors. In marked distinction to all other kappa-active agents examined which typically compete mu 1 binding with K i values under 1 nM, U50,488 competed mu 1 binding quite poorly (K i 370 nM). Thus, U50,488 is a highly selective kappa agent with very poor affinity for both subtypes of mu and delta receptors.