Thomas A Munro, Loren M Berry, Ashlee Van't Veer, Cécile Béguin, F Ivy Carroll, Zhiyang Zhao, William A Carlezon, Bruce M Cohen
BACKGROUND: Nor-BNI, GNTI and JDTic induce κ opioid antagonism that is delayed by hours and can persist for months. Other effects are transient. It has been proposed that these drugs may be slowly absorbed or distributed, and may dissolve in cell membranes, thus slowing elimination and prolonging their effects. Recent evidence suggests, instead, that they induce prolonged desensitization of the κ opioid receptor. METHODS: To evaluate these hypotheses, we measured relevant physicochemical properties of nor-BNI, GNTI and JDTic, and the timecourse of brain and plasma concentrations in mice after intraperitoneal administration (using LC-MS-MS)...
May 29, 2012: BMC Pharmacology