Naltrexone methylbromide

BeschreibungThe widespread efficacy of opioids in treating patients with moderate to severe acute and chronic pain is often accompanied by untoward side effects. In particular, opioid-induced bowel dysfunction is one of the more common and debilitating consequences afflicting up to 50% of patients. To counteract the peripherally-mediated adverse effects, opioid antagonists such as naloxone, naltrexone, and nalmephene are sometimes prescribed. The latest market entry exploits a strategic modification of naltrexone to lower its lipid solubility and increase its polarity: quaternization of the amine of naltrexone by methylation (methyl bromide) prevents crossing of the blood–brain barrier thereby creating an effective peripheral antagonist. Despite a loss of potency upon methylation, methylnaltrexone antagonizes opioid binding at m-opioid receptors with an IC50 of 70 nM. Its affinity for k-opioid receptors is approximately eightfold less (IC50＝ 575 nM) with no significant binding to d-opioid, orphanin, or non-opioid receptors. Methylnaltrexone bromide has been approved for the treatment of opioid-induced constipation in patients with advanced illness receiving palliative care.Regarding metabolism, methylnaltrexone bromide is eliminated primarily as intact drug (85% based on administered radioactivity) by slightly more renal than hepatic clearance.The most common adverse events were abdominal pain and flatulence followed by nausea, dizziness, and diarrhea.

VerwendenA metabolite of Naltrexone (N285750). Methylnaltrexone (MNTX), a selective μ-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract.