[Sobering up agents influencing toxicodynamics of ethanol].

The pathogenetic mechanisms of acute alcoholic intoxications are examined and is based the expediency of the search for the amethystic agents, which influence neurotransmitter systems. Promising should be considered the agents, which modulate GABA-systems (partial reverse agonists of benzodiazepine receptors), glutamate (antagonists of metabotropic receptors mGluR2/3), opioid neuropeptides (antagonists of opioid receptors), acetylcholine (reversible inhibitors of acetylcholinesterase and M-cholinoagonists), adenosine (selective antagonists of A(2A)-receptors). The amethystic effect manifest also the substances, which modify the second messengers systems (calcium, nitrergic and cascade of arachidonic acid). The most of the means examined possesses the moderate amethystic potential, and effectiveness is manifested predominantly during the preventive application.

[Substantiation of possibility of use GABA-receptor's chloride channel blockers for modelling of the temporal epilepsy].

In work the review of some clinik-morphological and pharmacological researches devoted to a temporal epilepsy and its experimental models is resulted. On the basis of the analysis of existing problems in working out antiepileptic drugs and in studying of mechanisms epilepsy necessity of development of new chronic experimental models of a temporal epilepsy is proved. The basic criteria of experimental model of a temporal epilepsy are generalised. It is shown that parametres of acute toxicity and the remote consequences of an intoxication convulsive agents from group GABA-receptor's chloride channel blockers correspond to the basic criteria a post-epistatus of model of a temporal epilepsy. The conclusion is presented on use possibility GABA-receptor's chloride channel blockers in quality agents for modelling of a temporal epilepsy.

[Involvement of brain neurotrophic factors in the pathogenesis of chemical dependences].

The involvement of brain neurotrophic factors (BNF) in the development and maintenance of the syndrome of psychic dependence on psychoactive substances is discussed. The implication of BNF in the pathogenesis of psychic dependence syndrome is supported by changes of the addictive power of psychostimulants, ethanol and morphine in conditions of metabolism modulation of these peptides as well as in rodents with defects in neurotrophin genes. Glial cell line derived BNF and tumor necrosis factor-alpha reduce the addictive potential of cocaine, methamphetamine, morphine and ethanol. Brain-derived neurotrophic factor, on the contrary, increases the addictive activity of cocaine suppressing the development of the syndrome of psychic dependence on ethanol. Thus, the BNF must be considered as an important group of neuroactive peptides implicated in the pathogenesis of chemical dependences.

[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.

The influence of ethanol on the functional status of GABA(A) receptors.

Gamma aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the mammalian brain. Its effects are realized via GABA(A), GABA(B), and GABA(C) receptors. GABA(A) is the most abundant type of GABA receptors. It consists of six classes of subunits, alpha, beta, gamma, delta, epsilon, and chi. Acute and chronic exposures to ethanol are accompanied by changes in structure and function of GABA(A) receptors. These changes may be a basis for altered behavior seen in alcoholism.

[Acamprosate--a novel treatment for alcoholism]. / Akamprosat--novoe lekarstvennoe sredstvo dlia lecheniia alkogolizma.

The properties of acamprosate (calcium acetylhomotaurate), a new remedy for the treatment of alcoholism, are reviewed. The efficacy of this drug has been verified by numerous clinical tests in West Europe. The pharmacological activity of acamprosate is related to the drug action upon central neuromediator systems. No side or addiction effects of the drug were reported. Data on the clinical and pharmacological characteristics of acamprosate are summarized.

[GABA-A receptor subunits and their reactions to neuropharmacological substances]. / Sub''edinitsy GAMK(A)-retseptorov i reaktsii na neirofarmakologicheskie veshchestva.

The structural-functional foundations of the heterogeneity of GABA(A)-receptors are discussed. The heterogeneity of the receptors was revealed by clone-formation methods. The existence of 5 classes of subunits (alpha, beta, gamma, delta, rho) was proved, each of them possessing isoforms (alpha 1-6, beta 1-4, gamma 1-4, delta, rho 1-2). Studies with expression of receptors showed the efficacy of neuroactive drugs of various groups (agonists, antagonists, reversible agonists of benzodiazepine receptors, barbiturates) to be dependent on the subunit composition of the complexes. Because of this, study of the properties of various recombinant receptors is very important for the advancement of neurobiology, neuropathology, neurochemistry, toxicology, and pharmacology.

[Current views on molecular structure of benzodiazepine receptors]. / Sovremennye predstavleniia o molekuliarnoi strukture benzodiazepinovykh retseptorov.

It is generally accepted that gamma-aminobutyric acid (GABA) is the most important inhibitory transmitter. It interacts with specific receptors. In the central nervous system of the vertebrates there are three types of GABA receptors: GABAA, GABAB, and GABAC receptors. Channel gating at GABAA receptors allosterically is modulated by a wide of neuroactive compounds, including benzodiazepine ligands. The structural and functional bases for the heterogeneity of benzodiazepine receptors are discussed. Investigations of the functional properties of GABAA and benzodiazepine receptors may contribute to progress in neurobiology, neuropathology, neurochemistry, toxicology, and pharmacology.

[The molecular aspects of the functional heterogeneity of the GABA receptors]. / Molekuliarnye aspekty funktsional'noi geterogennosti GAMK-retseptorov.

It is generally accepted that gamma-aminobutyric acid (GABA) is one of the main inhibitory transmitter in the mammalian brain. There are three types of GABA receptors in the vertebrata central nervous system: the GABAA, GABAB and GABAC receptors. The GABAA receptor is a GABA-gated Cl- channel and is the tetramer ore the pentamer made of some classes of subunit (alpha, beta, gamma, delta). GABAB receptors are not affiliated with Cl(-) ionophore. GABAB receptors appear to be coupled to Ca2+ and K+ channels of presynaptic membranes. It seems they regulate the release of neurotransmitters release. The structural and functional properties of GABA receptors are discussed.

[Functional state of glutamate receptors during treatment with ethanol]. / Funktsional'noe sostoianie retseptorov glutamata pri vozdeistviiakh étanolom.

A growing bulk of experimental data indicates that change of certain neurotransmitter receptors and voltage-dependent ion cannels are characteristic manifestations accompanying ethanol consumption. A likely target for ethanol effects is the glutamate receptors. Glutamate is one of major excitatory neurotransmitter in the mammalian brain. While the acute application of ethanol inhibits glutamate-induced cationic currents, chronic treatment with ethanol leads to an up-regulation of glutamate receptors.

[The effect of perftoran on the resistance of mice to GABA receptor antagonists and on the antidote activity of anticonvulsant agents]. / Vliianie perftorana na ustoichivost' myshei k antagonistam GAMK-retseptorov i antidotnuiu aktivnost' protivosudorozhnykh sredstv.

Perfluorane (a phenobarbital-type inducer of the microsomal enzyme system) raised the resistance of mice to the toxic effect of picrotoxin and bicucullin in 7 days after injection. The antidote effect of diazepam and phenobarbital increased under such conditions. In experiments in vitro a modulatory effect of perftorane on the central muscarine and benzodiazepine receptors was demonstrated.