メチルナルトレキソン臭化物

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The 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.