ATC Group: A06AH Peripheral opioid receptor antagonists

Alvimopan is a selective antagonist of the cloned human μ-opioid receptor with a Ki of 0.4 nM (0.2 ng/mL) and no measurable opioid-agonist effects in standard pharmacologic assays. The dissociation of [³H]-alvimopan from the human μ-opioid receptor is slower than that of other opioid ligands, consistent with its higher affinity for the receptor. At concentrations of 1 to 10 µM, alvimopan demonstrated no activity at any of over 70 non-opioid receptors, enzymes, and ion channels.

Methylnaltrexone bromide is a selective antagonist of opioid binding at the mu-receptor. As a quaternary amine, the ability of methylnaltrexone bromide to cross the blood-brain barrier is restricted. This allows methylnaltrexone bromide to function as a peripherally acting mu-opioid antagonist in tissues such as the gastrointestinal tract, without impacting opioid-mediated analgesic effects on the central nervous system.

Naldemedine is an antagonist of opioid binding at the mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without reversing the central nervous system (CNS)-mediated opioid effects.

Naloxegol is a PEGylated derivative of the mu-opioid receptor antagonist naloxone. PEGylation reduces naloxegol’s passive permeability and also renders the compound a substrate for the P-glycoprotein transporter. Naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system.