[Molecular aspects of pharmacological activity of naltrexone and naloxone]. / Molekuliarnye aspekty farmakologicheskoi aktivnosti naltreksona i naloksona.

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.

[Neurochemical basis of ultra rapid opioid detoxication]. / Neirokhimicheskie osnovy ul'trabystroi opiatnoi detoksikatsii.

Ultra rapid opioid detoxification (UROD) is a new technique with the use of mu-opioid receptor antagonists to precipitate withdrawal. The scientific literature on UROD techniques in opiate addicts are reviewed, but little has been published on its neurochemical aspects. It is discussed that exposure to naloxone ore naltrexone during UROD is associated with development of increasing in opioidergic neurotransmission. On the other hand, ultra rapid opioid detoxification can be accompanied by normalization of joined brain neurotransmitter systems: noradrenergic, serotoninergic, GABAergic, cholinergic and glutamatergic neurotransmission systems. The neurochemical aspects of the new method detoxification are discussed.