[Molecular aspects of pharmacological activity of naltrexone and naloxone]

Naltrexone and naloxone, being competitive antagonists of opioid receptors, have found therapeutic applications in medicine. The experiments with mutant receptors showed that many amino acid residues within transmembrane domains play an important role in binding these drugs. Using the site-directed mutagenesis technique, it was established that even single mutations (replacing single amino acid residues) can significantly modify the affinity of antagonists to receptors, sometimes even imparting agonist-like properties to the compounds studied. Chronic administration of naltrexone and naloxone leads to an increase in the density of opioid receptors and in the sensitivity to agonists. This hypersensitivity and overdose risk in heroin abusers after chromic naltrexone treatment are discussed.