U50,488: a kappa-selective agent with poor affinity for mu1 opiate binding sites.
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 (Ki 12 nM) when compared to both morphine-selective (mu2) or delta receptors (both Ki values greater than 500 nM) confirming earlier reports. However, these reports did not examine interactions with mu1 receptors. In marked distinction to all other kappa-active agents examined which typically compete mu1 binding with Ki values under 1 nM, U50,488 competed mu1 binding quite poorly (Ki 370 nM). Thus, U50,488 is a highly selective kappa agent with very poor affinity for both subtypes of mu and delta receptors.
Clark
J A
JA
Cotzias Laboratory of Neuro-Oncology Memorial Sloan-Kettering Cancer Center.
Pasternak
G W
GW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003496:Cyclazocine