Articles: narcotic-antagonists.
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Expert Rev Gastroenterol Hepatol · Nov 2014
ReviewNaloxegol for the treatment of opioid-induced constipation.
With increasing chronic opioid use, opioid-induced constipation (OIC) is a rapidly increasing clinical challenge. Naloxegol, an orally administered, peripherally-acting, µ-opioid receptor antagonist, was developed for the treatment of OIC. This drug profile summarizes published information and presentations at meetings on the effects of naloxegol in OIC. ⋯ Side effects were mainly gastrointestinal in origin, and usually transient and mild. A long-term safety study showed no new adverse events. The US FDA and EMA are currently evaluating the use of naloxegol in OIC.
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Observational Study
Buprenorphine-naloxone treatment in opioid dependence and risk of liver enzyme elevation: results from a 12-month observational study.
Some case series mention possible liver toxicity in opioid-dependent patients under buprenorphine treatment. ⋯ This study is in line with some recent studies and provides further evidence that buprenorphine-naloxone is relatively safe with respect to liver injury.
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The antagonist-bound crystal structure of the nociceptin receptor (NOP), from the opioid receptor family, was recently reported along with those of the other opioid receptors bound to opioid antagonists. We recently reported the first homology model of the 'active-state' of the NOP receptor, which when docked with 'agonist' ligands showed differences in the TM helices and residues, consistent with GPCR activation after agonist binding. In this study, we explored the use of the active-state NOP homology model for structure-based virtual screening to discover NOP ligands containing new chemical scaffolds. ⋯ Determination of the NOP receptor binding affinity of a selected set of top-scoring hits resulted in identification of several compounds with measurable binding affinity at the NOP receptor, one of which had a new chemotype for NOP receptor binding. The hybrid ligand-based and structure-based methodology demonstrates an effective approach for virtual screening that leverages existing SAR and receptor structure information for identifying novel hits for NOP receptor binding. The refined active-state NOP homology models obtained from the enrichment studies can be further used for structure-based optimization of these new chemotypes to obtain potent and selective NOP receptor ligands for therapeutic development.
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Randomized Controlled Trial
Peripheral opioid receptor blockade increases postoperative morphine demands - a randomized, double-blind, placebo-controlled trial.
Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) would increase the patients' demand for morphine to achieve satisfactory postoperative pain relief. ⋯ Secondary endpoints were similar in all groups (P>.05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.