Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity.

ABSTRACT:

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).

Results

In each case, plasma levels were maximal within 30 min and declined by >80% within four hours, correlating well with previo

SUBMITTER: Munro TA 

PROVIDER: S-EPMC3411462 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature