[Effect of anticonvulsants on the nitric oxide system].

The effect of phenobarbital, carbamazepine, valproate sodium, depakine, topiramate and lamotrigine on the content of NO and NO-synthase activity in white rat brain tissues has been studied. It was established that the action of carbamazepine, valproate sodium, topiramate and lamotrigine decreases the activity of NO-synthase and the level of NO in the brain tissues. The amount of NO does not change while NO-synthase activity increases with the introduction of phenobarbital. The involvement of nitric oxide in the mechanism of action of the studied anticonvulsant drugs is discussed.

[Anticonvulsive activity of antiepileptic drugs and quantum-chemical modelling of their interaction with GABA(A) receptor]. / Antikonvul'santnaia aktivnost' protivoépilepticheskikh preparatov i kvantovo-khimicheskoe modelirovanie ikh vzaimodeistviia s retseptorom GAMK(A).

The results of experimental analysis of the clinical activity of the antiepileptic drugs' (Phenobarbital, Carbamazepine, Valproic acid, Lamotrigine, Topiramate, Felbamate) widely used in clinic, that was carried out using the standard convulsion test with bicuculline in vivo were compared with characteristics of these drugs' interaction with the key aminoacids of GABA(A) receptor calculated by quantum chemical method (program HyperChem7, semi-empirical method AM1 technique). The correlation between the activity of the drugs in the experiment in vivo and energy of system's interaction of the drugs with aminoacid residue Thr201-Thr202-Gly203- Ala204-Tyr205-Pro206 was found out.

[The neuromediator mechanisms of the action of korazol]. / Neiromediatornye mekhanizmy deistviia korazola.

Present paper analyses the known neurotropic effects of GABA-lytic agent corazole (pentylentetrazole), including both "traditional" anxiogenic convulsant properties at systemic doses > 10 mg/kg and reported recently its anxiolytic effects in doses < 2 mg/kg. Understanding the relations between anxiogenic and convulsant properties of a drug, we studied possible effects of pre-treatment by "anxiolytic" dose of corazole (1 mg/kg i.p.) on corazole-induced convulsions at systemic dose of 90 mg/kg in mice. Despite the expectations, small dose of corazole (1 mg/kg) did not reduce convulsions but rather increased them. This result challenges the hypothesis of possible GABA-ergic mechanisms of "positive" effects of corazole in small doses. The potentiation effects were particularly marked for Straube symptom. The symptom is believed to reflect the excitation of inhibitory spinal motoneurons responsible for tail muscles tonus. Perhaps, corazole at a systemic dose of 1 mg/kg can influence separately on the GABA-receptors located in spinal motoneurons or cells of origin of supruspinal pathways. Other possible neuromediator (including glycine-, glytamat-, opioid-, choline- and monoaminergic) mechanisms for corazole action are discussed to illustrate the mosaic of its neurotropic properties.

[Synthesis and study of biological activity of stereoisomeric dipeptides containing tyrosine and arginine residues]. / Sintez i issledovanie biologicheskoi aktivnosti stereoizomernykh dipeptidov, soderzhashchikh ostatki tirozina i arginina.

Series of methyl esters of stereoisomeric dipeptides of the sequences Tyr-Arg and Arg-Tyr has been synthesized by classic methods of the peptide chemistry. The study of their reactivity towards thrombin and trypsin has shown that the kinetic parameters of enzyme-catalyzed hydrolyses of stereoisomeric compounds differ in values essentially. Testing the synthetic peptides on analgic effect, on inhibition of the reaction fibrinogen with thrombin or on influence upon the process of fibrin-monomer polymerization has shown that these biological effects depend on peptide structure and on configuration of amino acid residues forming the peptides.

[Free radical mechanisms of memory disorders of toxic origin and experimental therapy of the condition]. / Svobodnoradikal'nye mekhanizmy narushenii pamiati toksicheskogo geneza i éksperimental'naia terapiia étogo sostoianiia.

Influence of the pesticides deltametrin and dichlophos on memory processes and activity of the antioxidative enzymes superoxide dismutase (SOD) and catalase in the brain and blood of female rats was studied. Xenobiotics disturbed processes of formation and storage of signs of memory, which were tested in the conditional reaction of passive avoidance and in the conditional reaction of active avoidance; they also lowered SOD activity (but not catalase) in the brain (deltametrin by 25%, dichlophos by 21%) 3 h after their injection to the animals. Indices of SOD activity and blood catalase didn't change. SOD inhibition is suggested to be a result of the action of biotransformation product of deltametrin and dichlophos molecules on it, since in in vitro experiments pesticides don't exert influence on the inhibition kinetics of epinephrine autooxidation by brain homogenates. Prophylactic use of alpha-tocopherol or unithiol optimizes the processes of learning and memory in rats, intoxicated with these toxicants; a more marked antiamnestic, effect is observed in the combined injection of these preparations.

[Activity of antioxidant defense enzymes and the state of lipid peroxidation in the rat brain in decis and dichlofos poisoning]. / Aktivnost' fermentov antioksidantnoi zashchity i sostoianie protsessov perekisnogo okisleniia lipidov v mozge krys pri intoksikatsii detsisom i dikhlofosom.

The activity of the antioxidant system enzymes--superoxide dismutase (SOD) and catalase and lipids peroxidation in the rat brain under deltametrin and dichlorvos intoxication has been studied in vivo. It was shown that both xenobiotics lowered SOD activity 30 minutes after the injection. Accumulation of superoxide ions as a result of inhibition of SOD activity may stimulate lipid peroxidation of biological membranes. Activation of lipid peroxidation in the rat brain in vivo under dichlorvos and deltametrin intoxication was established. It was shown in the in vitro experiments that deltametrin (but not dichlorvos) stimulated NADPH-induced lipid peroxidation.

[Pharmacologic analysis of the free radical mechanism of poisoning-induced memory disorders]. / Farmakologicheskii analiz svobodnoradikal'nogo mekhanizma intoksikatsionnykh narushenii pamiati.

Ethylene glycol, the pyrethroid pesticide deltametrin, and the m-cholinolytics atropine and scopolamine disturb the formation and storage of signs of memory in rats appraised in the test for conditional reaction of passive and active avoidance. The antioxidants alpha-tocopherol and sodium selenite, the nootropic agent piracetam, and the amino acid L-tryptophan prevent amnesia. Spectrometry of optic density in a "diphenylpicrylhydrazil-drug" model system showed the existence of anti-radical activity in piracetam and L-tryptophan. It is suggested that the anti-amnestic efficacy of piracetam and L-tryptophan is associated, to a certain measure, with their antioxidant properties.

Functional role of the neurospecific S-100 protein in the processes of memory.

The change in the content of S-100 protein in the brain in the presence of learning and an amnestic influence (administration of an M-cholinolytic), taking interhemispheric asymmetry into account, was studied in experiments on white rats. The action of S-100 protein and of an antiserum to this protein on the learned behavior of the rats were also investigated. It was established that the level of S-100 protein increases in the left and right hemispheres in the process of the development of an alimentary conditioned reflex. The disruption induced by the cholinolytic of the processes of the development of conditioned reflexes is accompanied by a decrease in the content of S-100 protein in the brain. Intracisternal administration of an M-cholinolytic and an antiserum to S-100 protein mutually potentiates their amnestic effect.

[The biochemical antagonism of cholinolytics and cholinomimetics at the level of the opiate system]. / Biokhimicheskii antagonizm kholinolitikov i kholinomimetikov na urovne opiatnoi sistemy.

The experiments on albino rats with the use of the radioimmunoassay showed that M-cholinoblockers (atropine, amizil, glypine) decrease the contents of enkephalins and beta-endorphin in the brain and blood whereas M-cholinomimetics (arecoline, nicotine, physostigmine) increase the level of opioid neuropeptides. This suggested that between cholinoblockers and cholinomimetics there is not only functional but also biochemical antagonism at the level of the opiate system. In addition, the statement is developed that toxic effects of cholinoblockers and cholinomimetics are largely related to disturbances of metabolism and function of opioid neuropeptides.

[The functional role of neurospecific protein S-100 in memory processes]. / Funktsional'naia rol' neirospetsificheskogo belka S-100 v protsessakh pamiati.

Elaboration of alimentary conditioned reflex in rats is accompanied by an increase of the level of protein S-100 in the left and right cerebral hemispheres. Amnestic factor M-cholinolytic atropine disturbs the elaborated habit and simultaneously decreases the quantity of protein S-100 up to the level of unlearned animals. The elaboration of conditioned reflex of passive avoidance does not change the content of protein S-100 in the rats brain. Intracisternal injection of antiserum to protein S-100 has an expressed amnestic action. Intracisternal injection of protein S-100 against the background of amnestic action of cholinolytic does not lead to restoration of memory. The cholinolytic and antiserum to protein S-100 mutually potentiate the amnestic effect.

[The analgesic activity of coordination compounds of methionine enkephalin with divalent metals]. / Anal'geticheskaia aktivnost' koordinatsionnykh soedinenii metionin-énkefalina s dvukhvalentnymi metallami.

Coordination compounds of methenkephalin with transition metals: copper, cobalt, nickel and zinc were shown to be superior to morphine by the analgesic activity and to morphine and methenkephalin by the duration of the analgesic effect. A more stable relationship between opiate receptors and copper-containing methenkephalin was shown in the experiments on the isolated neuronal membrane.

[The serotoninergic mechanism and the experimental therapy of sleep disorders in desynchronization]. / Serotoninergicheskii mekhanizm i éksperimental'naia terapiia narushenii sna pri desinkhronoze.

The authors studied the dynamics of changes in the serotonin content in the brain of albino rats in development of experimental neurosis along the type of desynchronization and under the effect of essential amino acid L-tryptophan. It was found that disturbance in the sleep-awake cycle in desynchronization is attended with decrease in the serotonin level in the hemispheres and brain stem and leveling out the interhemispheric asymmetry. Injection of 80 mg/kg L-tryptophan in this condition leads to increase of the brain serotonin content and restoration of the normal physiological structure of the sleep-awake cycle.

[Humoral factors of regulation of water-salt metabolism in experimental traumatic brain edema]. / Gumoral'nye faktory reguliatsii vodno-solevogo obmena pri éksperimental'nom travmaticheskom oteke mozga.

Experiments on albino rats with experimental traumatic brain edema were made to study humoral factors of water-salt metabolism regulation: neuropeptides (vasopressin, angiotensin-II as well as aldosterone in the brain and body tissues using radioimmune analysis. Besides, the effect of natriuretic hormone on brain edema was assessed. It was established in preliminary investigations that the highest water content in the brain was recorded on the third day after the suffering of a craniocerebral injury. During the same time, the injured hemisphere showed an increase of sodium ions. The level of vasopressin in cerebral hemispheres rose whereas in the pituitary and blood plasma, it decreased. The injured hemisphere manifested a dramatic increase of angiotensin content. The craniocerebral injury gave rise to aldosterone secretion enhancement and to its elevation in the plasma and brain. The marked and non-uniform alterations in factors of water-salt metabolism and of the vascular tone regulation are important components in the pathogenesis of brain edema, which determines goal-oriented approaches to the search of agents for the treatment of the pathology under consideration.

[Interhemisphere asymmetry of neuromediators in the brain of albino rats]. / Mezhpolusharnaia aimmetriia neiromediatorov v mozgu belykh krys.

The presence of interhemispherical asymmetry in the content of acetylcholine, norepinephrine, epinephrine, and dopamine is shown in experiments on albino rats. In this case no differences are observed in the acetylcholinesterase, monoamineoxidase and dopadecarboxylase activities in the left and right hemispheres. An assumption is advanced that neuromediatory interhemispherical asymmetry of the brain is connected with interhemispherical peculiarities of their storage, excretion and inverse capture. The data obtained should be taken into account in the study of pathogenesis of nervous-physical diseases and in the study of the mechanism of neurotropic drugs action.

[Effect of central cholinolytics on opioid neuropeptide levels in the animal brain]. / Vliianie tsentral'nykh kholinolitikov na soderzhanie opioidnykh neiropeptidov v mozgu zhivotnykh.

Atropin, amizyl, glypin are shown to decrease the level of methionine- and leucin-enkefalins in the rat brain. The effect depends on the dose of cholinolytics.

[Isolation of opioid neuropeptides from the brain and blood and their quantitative determination by a radioimmunological method]. / Vydelenie opioidnykh neiropeptidov iz mozga i krovi i ikh kolichestvennoe opredelenie radioimmunologicheskim metodom.

The content of beta-endorphin, methionine- and leucine-enkephalins was determined in the brain and blood of albino mongrel rats. The unified scheme is suggested for releasing opioid neuropeptides from the brain tissue and blood.