[Study of neuroprotective, antihypoxic and antiamnesic effects of new mixture of tripeptides].

A new mixture of tripeptides (NMT: H-Lys-Asp-Glu-OH, H-Asp-Glu-Pro-OH, H-Asp-Glu-Arg-OH) in doses of 150 and 300 mg/kg per day produces clearly pronounced neuroprotective effect in rats with brain ischemia and decreases neurologic deficiency 1.1 times more effectively than reference drug semax. NMT (10, 50 and 150 mg/kg) had marked antihypoxic effect on mice in hermetic and altitude chamber.

[Study of some pharmacological properties of a new adenine derivative].

It is established that the new compound, 9-[2-(4-isopropylphenoxy)ethyl]adenine (9-IPE-adenine) in a dose of 10 mg/kg per day produces neuroprotective effect in rats with brain ischemia model. 9-IPE-adenine decreased the neurologic deficiency 1.2 times more effectively (p < 0.

[Investigation into the vestibular protective properties of melatoninergic agents].

Experiments with rats showed that melatonin (2.5 mg/kg) produces a distinct vestibular protective effect excelling promethazine (50 mg/kg) as a reference agent, and also antidepressant agomelatine (5 mg/kg) as another melatoninergic agent. Lusindol, a blocker of MT1/MT2-receptors (2.

[The antiamnestic effect of nootropic substances in rats].

It has been established in experiments in rats that some nootropic substances (oxyracetam, aniracetam, nooglutil, mexidol, new 3-hydroxypyridine derivative SK-170, piracetam and noopept) produce marked antiamnestic effect on various models of amnesia (induced by microwave irradiation, acute hypoxia, and motion sickness). At the same time, meclophenoxate exhibited antiamnestic effect in the first and second models of amnesia, while 9-aminoacridine derivative HTOS-404 was only effective in the model of amnesia caused by microwave irradiation. The antiamnestic effect of nooglutil and SK-170 was caused to a significant degree by activation of non-NMDA receptors of excitatory amino acids (generally AMPA receptors), while the effect of mexidol was related to GABA(A) receptors.

[Effects of vestibuloprotectors mexidol and melatonin on animal cerebellum].

In experiments with cats, air-assisted microinjections of mexidol and melatonin had a direct effect on 71-81% Purkinje cells inducing the inhibitory response 4.2-6.3 times more often than exiting.

[Experimental evaluation of actoprotective activity of nitrogen-containing heterocyclic compounds derivatives in extreme conditions].

In experiments on nonlinear male mice the ability of new derivatives of nitrogen-containing heterocyclic compounds to increase the physical working capacity in conditions of hyperthermia, hypothermia and acute normobaric hypoxia and hypercapnia has been investigated. It is established, that pyridine derivative IBHF-11 has more expressed positive action in the said conditions. It provided increase of the working capacity of animals at all kinds of extreme influence, and the value of positive action was comparable, and in conditions of acute normobaric hypoxia and hypercapnia exceeded those at the reference products bemitil and bromantan.

[On the mechanism of ikaron-1 anti-naupathia action].

Pneumomicroinjection of vestibuloprotector ikaron-1 (Russia) in specific neurons of the medial vestibular nucleus (MVN) was studied in cats immobilized by muscle relaxants using microelectrode devices. The original preparation had a direct effect on the majority of MVN neurons (95 %). Thirty four neurons of 37 cells (92 %) developed an inhibitory response, only one cell (3 %) was activated and 2 neurons (5 %) were areactive.

[Analgesic effect of succinate-containing preparations].

It was established that mexidol (100 mg/kg, i.v.) in contrast to cytoflavin (1 ml/kg, i.

[Comparative studies of antihypoxic, neuroprotective and analgesic action of succinate-containing drugs].

Experiments with mice showed that, unlike reamberin (100 mg/kg), mexidol (100 mg/kg) and cytoflavin (1 ml/kg) act as antihypoxants in pressure and hermetic chambers but not in case of acute hemic and histotoxic hypoxia. Amtisol succinate (100 mg/kg), a reference antihypoxant, excels the other tried succinate-containing drugs in all models of acute hypoxia except the hermetic chamber. In addition, the neuroprotective action of mexidol (100 mg/kg/d) and cytoflavin (100 ml/kg/d) in rats with induced ischemic stroke which was stronger than that of reamberin and amtisol succinate (100 mg/kg/d).

[Studies on actoprotective and antihypoxic properties of new succinate-containing benzothiazole derivatives].

Experiments with mice demonstrated that in contrast to the preparations for comparison (mexidol and reference antihypoxant succinate amtisol at a dose of 1-100 mg/kg) new succinate-containing derivatives of benzothiazole BTI-2 (0.5-5 mg/kg), BTI-3 (0.1, 0.

[Comparative study of the influence of succinate-containing preparations on mitochondrial respiration in rat brain cells].

It has been established by polarographic measurements that preparations containing succinate, such as cytoflavin (0.85 mM succinate), mexidol, and amtizol succinate (at a concentration of 0.85 mM) but not reamberin (0.

[Electrophysiological study of the mechanism of mexidol action].

It has been found that mexidol (5 mM) significantly (96 +/- 2%) depressed excitatory postsynaptic current caused by step depolarization in neurons of medial vestibular nucleus of medulla oblongata slices in young (aged 13 - 17 days) male albino rats. In addition, mexidol (2,5 - 5 mM) depressed by 94 +/- 3% excitatory postsynaptic current caused by Shaffer collaterals stimulation of CA1 pyramidal neurons of hippocampal slices in young rats. Complex MK-801 (non-competitive antagonist of NMDA receptors), in contrast to CNQX (competitive AMPA receptor antagonist), considerably decreased the depressant effect of the drug in both brain structures.

[Actiprotective and antihypoxic action of new heteroaromatic antioxidants].

Expernents with mice showed that most of 15 new heteroaromatic antioxidant compounds possess aciprotective and antixopixic properties. Based on results of treadmill and swimming tests, actiprotective action of IBKhF-1, 11 and 14 surpassed greatly bemythil and bromanthane in ordinary conditions. Inhibitor of gluconeogenase tryptophan cancelled largely the stimulatting action of highly effective and active IBKhF-1, 2 and 11 on physical performance during treadmill exercise.

[Investigation of anti-hypoxic action of 3-hydroxypyridine derivatives in animals with some types of experimental pathology].

Experiments with occlusion of the common carotid artery in mice demonstrated that, unlike mexidol and SK-170, single injection of new derivatives of 3-hydroxypyridine (3-HP) SK-100 and IBKhF-2, and semax have an anti-hypoxic action on the model of acute normobaric hypoxia with hypercapnia. In analogous experiments with rats the distinct anti-hypoxic action was produced by 4 new 3-HP derivatives (SK-100, SK-170, IBKhF-22 at the dose of 100 mg/kg and IBKhF-2 at the doses of 10 and 30 mg/kg--extension of life span by 25-39%), mexidol (100 mg/kg) and reference-class antihypoxant amtisol (30 mg/kg, life span expansion by 19 and 27%, respectively). A series of experiments with rats with acute pancreatitis, a distinct anti-hypoxic action was shown by SK-100, SK-170 at 100 mg/kg and IBKhF at 10 and 30 mg/kg (life span extension by 26-40%), mexidol (100 mg/kg) and amtisol (30 mg/kg) which extended life span by 17 and 22%, respectively.

[On the mechanism of antimotion sickness effects of mexidol].

The path-clamp method used within the whole-cell configuration in experiments with convoluted medullar oblongata sections obtained from white mongrel male rats aged 13 to 17 days evidenced that 5 mV of mexidol caused 96 +/- 2% inhibition of the excitation postsynaptic current in neurons of the medial vestibular nucleus generated by the depolarization step of 10 mV (holding potential = -70 my). This means that the antimotion sickness effect of mexidol has its origin in the ion mechanisms with involvement of the glutamate- and GABAergic components, primarily inhibition of ion currents through channels of the NMDA-receptor complex.

[Effects of different neuromediators and regulatory peptides on the impulse activity of neurons in vestibular zone-I of the cerebral cortex].

Microelectrodes and micro-iontophoresis of physiologically active substances in experiments with cats immobilized by muscle relaxants made it apparent that different classical neuromediators (acetylcholine, norepinephrine, GABA and others) and regulatory peptides (enkephalins, thyrotropin-releasing hormone, vasoactive intestinal peptide (VIP), somatostatin (SS) and others) are capable to influence directly 68 to 100% of neurons in vestibular zone-I of the cerebral cortex. In the presence of L-glutamate, the inhibiting effect of enkephalins, VIP and SS on the neurons impulse activity was essentially unaltered. Also it was shown that enkephalins, VIP and SS are potent to augment the inhibiting effect of GABA and glycine.

[Antihypoxic and antiamnesic effects of mexidol and semax].

Upon single administration, mexidol and semax only in doses of 100 and 0.05 mg/kg, respectively, produced an antihypoxic effect on mice in the altitude chamber and hermetic chamber tests. Preventive course administration of mexidol and semax for 6 days gave significant antihypoxic effect on the model of acute hypobaric hypoxia in mice in doses of 75 and 0.

[Evaluation of antihypoxic and antiamnemonic effects of mexicor in animals].

In experiments with mice closed in airtight and altitude chambers mexicor effectiveness against hypoxia was evident only at the dose of 100 mg/kg; effect was nil against acute hemic and histotoxic hypoxia. The reference antihypoxic substance (amtisol succinate, 25-100 mg/kg) excelled mexicor in all models of acute hypoxia. In the model of cerebral infarct in rats, the mexicor neuroprotective effect at the doses from 12.

[Effects of various neuromediators and regulatory peptides on the impulse activity of neurons in the lateral vestibular nucleus].

The myoelectrode technique and microiontophoresis of physiologically active substances were applied to cats immobilized with neuromuscular relaxant to show that the classic neuromediators (acetylcholine, norepinephrine, GABA etc.) and regulatory peptides (enkephalins, TRHs, vasoactive intestinal peptide (VIP), somatostatin (SS) and others) can influence directly most neurons (58 to 100%) in the lateral vestibular nucleus (LVN). Enkephalins, VIP and SS retained largely their inhibitory effect on the neuron impulse activity in the presence of L-glutamate.

[Effect of semax and mexidol on brain ischemia models in rats].

It was established that semax and mexidol significantly reduced neurological deficiency and increased the survival in rats with model brain ischemia induced by the bilateral ligation of common carotid arteries. Mexidol exhibited a linear dose-effect relationship (in a range of doses from 30 to 120 mg/kg per day), while the effect of semax decreased with increasing dose (in a dose range from 0.3 to 1.

[Modification by various neuromediators and regulatory peptides of the impulsation activity of neurons in the medial vestibular nucleus].

Cats were immobilized with myorelaxation agents to apply the microelectrode technique and microlonophoresis of physiologically active substances. As a result it was shown that various classic neuromediators (GABA, taurine and others) and regulatory peptides (vasoactive intestinal peptide (VIP), somatostatine (SS) and others) have effect on the majority (62 to 100%) of neurons in the medial vestibular nucleus. In the presence of L-glutamate VIP and SS CC retained essentially their inhibitory effect on the neurons impulse activity.

[Protective action of radioprotectors and shielding against high-energy protons in experiments with rats].

Experiments with male rats were staged to study effectiveness of radioprotectors of two classes of chemical compounds (aminothiols--cystamine and indolyl alkylamines--mexamine and indralin) against high-energy protons (120 MeV) at a minimal absolutely lethal dose (10 Gy) and more than lethal doses (11.0-14.0 Gy).

[Mexidol effects in extreme conditions (experiments with animals)].

In extreme conditions like a new situation, bright light, open space, immobilization, height (the open field and lifted cruciform labyrinth test) and a conflict between an unavoidable action and fear of painful mexidol at the doses of 50 and 100 mg/kg of a body weight eliminates anxiety and fear in rats, recovers adequate reactions and the orientative-trying behavior, and lessens aggressiveness. Mexidol extends life span of mice in acute hypoxic conditions. Mexidol is highly competitive with diazepam as an anti-stress agent and excels it as an anti-hypoxic agent; in contrast to diazepam, mexidol does not cause sedation and myorelaxation.