Opioids have a long history of therapeutic use as a remedy for various pain states ranging from mild acute nociceptive pain to unbearable chronic advanced or end-stage disease pain. Analgesia produced by classical opioids is mediated extensively by binding to opioid receptors located in the brain or the spinal cord. Nevertheless, opioid receptors are also expressed outside the CNS in the periph...

BACKGROUND We assessed the analgesic efficacy of parecoxib, acetaminophen, and the combination of both compared with placebo in patients undergoing elective thyroid or parathyroid surgery. METHODS We randomized 140 patients to receive one of the following i.v. treatments using a double-blinded double-dummy technique: placebo, 80 mg 24 h(-1) parecoxib, 5 g 24 h(-1) acetaminophen, or 80 mg pare...

PURPOSE Patients treated with opioid drugs for cancer pain experience different relief responses, raising the possibility that genetic factors play a role in opioid therapy outcome. In this study, we tested the hypothesis that genetic variations may control individual response to opioid drugs in cancer patients. EXPERIMENTAL DESIGN We tested 1 million single-nucleotide polymorphisms (SNP) in ...

Morphine and other mu opioids mimic and/or modulate the discriminative stimulus (DS) effects of cocaine, possibly reflecting mutual stimulation of mesolimbic dopamine activity. Less is known about the capacity of cocaine and related stimulants to modulate the DS effects of morphine. The present study investigated the effects of cocaine, amphetamine, and reference drugs, administered alone and w...

It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes. In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs. This minireview summarizes these re...

Sigma receptors are protein chaperones with the unexpected characteristic of being activated by ligand binding. As such, they represent intriguing new targets for potential drug development. a chaperone, these “receptors” escort proteins from endoplasmic reticulum to their destinations and act correct misfolded proteins. The two subtypes sigma receptors, named σ1 σ2, markedly distinct each othe...

Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health ...

The μ-opioid receptor (MOP) is a subtype that belongs to the superfamily of 7-transmembranespanning G-protein-coupled receptors. Pharmacological studies with gene-knockout mice show that MOP is a major target for the clinically important opioid drugs, such as morphine and fentanyl, and it appears to play critical roles in the mediation of the major effects of these opioid drugs, including analg...

Accumulating evidence suggests that glutamate, as one of the most important excitatory neurotransmitters in the brain, plays a key role in drug addiction including opioid addiction. There is substantial evidence for glutamatergic projections into mesocorticolimbic dopaminergic neurons, which are associated with opioid psychological dependence and are also the key regions of enhancement effect. ...

We have examined the endocytic trafficking of epitope-tagged delta and mu opioid receptors expressed in human embryonic kidney (HEK) 293 cells. These receptors are activated by peptide agonists (enkephalins) as well as by the alkaloid agonist drugs etorphine and morphine. Enkephalins and etorphine cause opioid receptors to internalize rapidly (t1/2 approximately 6 min) by a mechanism similar to...