1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to investigate their structure-activity relationships as inhibitors of the human and murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhi...

BACKGROUND Clinical and experimental data suggested a long delay between the plasma concentration versus time course of morphine-6-glucuronide and the time course of its central opioid effects. This study was aimed at the quantification of the transfer half-life (t(1/2,ke0)) of this delay. METHODS Pupil size was used as a measure of central opioid effect. Eight healthy volunteers (four men, f...

by Kimberly T. Tsutsui, M.S. Washington State University May 2010 Chair: Rebecca. M. Craft Use of anabolic-androgenic steroids (AAS) has been anecdotally associated with pain reduction as well as opioid abuse. The purpose of the current study was to investigate the effects of AAS on nociception and morphine antinociception in acute pain models, as well as on chronic nociception in an arthritis ...

Receptor binding studies of 5,14-O-dimethyloxymorphone (14methoxymetopon) in brain membranes have established its high affinity for -binding sites, but its analgesic potency far exceeds the modest increase in binding affinity relative to other opioids. The current study has established the selectivity of [H]14-methoxymetopon for sites in calf striatal membranes and for a number of full-length s...

Common neurobiological substrates contribute to the progressively increased behavioral effects (i.e., sensitization) that occur with repeated intermittent treatments of cocaine and morphine. Consequently, repeated exposure to cocaine can augment responding to morphine (termed cross-sensitization). Drug-induced sensitization in rats may model aspects of the dysfunction in motivation that are imp...

Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonis...

SAFE PRACTICE RECOMMENDATION: Here are some steps to take to reduce the risk of patient harm. 1. Access to hydromorphone should be limited. Stock amounts of hydromorphone should be reduced, whenever possible, and should be eliminated from floor stock entirely if usage is low. The health facility where the error occurred has now removed hydromorphone from every ED in the health care region. If t...

( )-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl) is a novel -opioid receptor (MOR) agonist (Ki 0.1 M; relative efficacy compared with morphine 88% in a [S]guanosine 5 -3-O-(thio)triphosphate binding assay) and NE reuptake inhibitor (Ki 0.5 M for synaptosomal reuptake inhibition). In vivo intracerebral microdialysis showed that tapentadol, in contrast...