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Biomedical subjects

R U Ostrovskaia

Publications and source records attributed to R U Ostrovskaia.

At least 37 records · Page 2Linked to original sources
PubMed1987

[Behavioral and electrophysiologic characteristics of a peptide analog of piracetam--L-pyroglutamyl-D-alanine amide].

The effect of L-pyroglutamyl-L-alanine amide, a structural analog of nootropil, was studied in the passive and active conditioned avoidance tests in rats. The compound (1 mg/kg, i. p.) was shown to be able to improve the performance in the shuttle-box. This effect is selective because it is not followed by psychomotor stimulation. In experiments on undertrained animals in passive avoidance test the compound reveals its positive amnestic effect with its administration prior to, immediately after learning and prior to testing. This provides the evidence that the dipeptide activates all the phases of memory formation. The compound raises the amplitude of transcallosal responses in temporal associative area and S-1 and increases facilitation phase in the recovery cycle, being inactive in respect to primary somatosensory evoked responses in S-1. All the data obtained suggest the nootropil-like effect of the dipeptide. The analysis of the dipeptide by MR-spectrometry reveals its stability in the presence of serum or enterocyte enzymes.

Animals↗
PubMed1986

[Piracetam correction of deficient GABA-ergic inhibition due to early postnatal exposure to cycloheximide].

Cycloheximide, administered to 7-day-old rats, caused the delay of CNS activity changes in grown-up rats. The animals showed impaired memory function, expressed in the decrease of habituation in the "open field" test, and the alteration of passive avoidance reflex. The increased number of intersignal reactions due to hypermotility was found during elaboration of avoidance reflex. The analysis of evoked potential recovery revealed the deficiency of GABA-ergic inhibition in the neocortex. Piracetam was shown to prevent completely behavioural disturbances and deficiency of GABA-ergic processes in grown-up animals.

Animals↗
PubMed1986

[Mechanism of the antidepressive and learning-stimulating effects of thyroliberin and its analogs].

To define the role of different fragments of TRF molecule in its neurotropic activity a number of newly synthesized dipeptides of pyroglutamic acid with beta-alanine residue, GABA or GABA ester have been studied. The compounds were compared with TRF in their ability to influence spontaneous or amphetamine-stimulated locomotor activity in mice and to affect the elaboration of passive avoidance reflex in rats. Unlike TRF, the pyroglutamate dipeptides studied were shown to exhibit no activity in amphetamine potentiation test, thus providing additional evidence of the importance ofthe "histidylproline" fragment in TRF antidepressant effect. On the other hand, the above pyroglutamate derivatives caused a pronounced improvement in the learning abilities of under-trained rats. These dipeptides were shown to be more active in this test than TRF. This suggests the important role of pyroglutamyl moiety in the stimulation of the learning processes.

Animals↗
PubMed1985

[Antagonism of RO 15-1788 with benzodiazepines in the effect on motivated aggression and the action of analgesics].

The influence of Ro 15-1788 and bicuculline on the action of GABA-positive drugs (muscimol), GABA cethyl ester, piracetam and depakine and benzodiazepine tranquilizers (diazepam, phenazepam) on motivated aggression has been studied. It has been shown that Ro 15-1788 which has a weak antiaggressive effect selectively antagonizes the anti-aggressive effect of tranquilizers but not that of GABA-positive drugs. Bicuculline antagonizes antiaggressive activity of the drugs of both types. The action of these antagonists on the effect of the drugs under study as regards the analgetic activity of morphine was also studied. It has been shown that Ro 15-1788 antagonizes the potentiation of morphine analgesia caused by diazepam. At the same time Ro 15-1788 does not influence morphine analgesia potentiated by muscimol. Bicuculline removes the potentiation of morphine analgesia caused both by diazepam and muscimol it is concluded that bicuculline-sensitive GABA receptors modulate the antiaggressive effect of benzodiazepines and their influence on the analgetic action of opiates.

Aggression↗
PubMed1985

[Antagonism of piracetam with proline in relation to mnestic effects].

Based on the authors' previous data showing that the lipophylic cethyl group promotes the penetration of amino acids through the blood-brain barrier, proline cethyl ester was synthesized and studied as a neuropharmacological tool. The substance administered to rats systemically (intraperitoneally) was shown to be able to provoke a deep amnesia when tested by the conditioned avoidance performance. Piracetam abolished the amnestic effect of proline cethyl ester while sodium hydroxybutyrate administered in the dosage range provoking the nootropic effect did not change that amnesia. The data suggest that proline may be considered as one of the possible endogenous amnestic factors. The close structural similarity of the piracetam cyclic fragment to proline, which resulted in their competition, appears to be one of the reasons for piracetam antiamnestic activity.

Animals↗
PubMed1985

[Effect of piracetam derivatives on antibody formation].

Immunomodulatory effects of piracetam and a number of its derivatives were studied in mice. It was shown that multiple injections of such substances at a dose of 50-200 mg/kg change the amount of antibody-forming cells in the spleen of animals immunized with sheep red blood cells. The dose of 200 mg/kg was the most effective one, with the direction of immunomodulatory activity depending on the chemical composition of the compounds. Thus joining of phenol radical to piracetam molecule strengthened immunosuppression, and vice versa insertion of hydrazide group led to stimulation of antibody formation. It is stressed that immunosuppressive effect of piracetam must be taken into consideration during the clinical use of the drug.

Animals↗
PubMed1984

[Effect of opiate receptor agonists and antagonists on the resistance of animals to hypoxic hypoxia].

The effects of morphine, a series of synthetic enkephalin analogs and antagonists of narcotic analgesics on the animals' survival rate under hypoxic hypoxia were studied in experiments on mice, rabbits, and cats. It was shown that the agonists of mu-opiate receptors, morphine, FK 33-824 (Tyr-D-Ala-Gly-MePhe-Met-(O)-ol, Tyr-D-Ala-Gly-Phe-(NO2)-NH2 and Tyr-D-Ala-Gly-MePhe-Gly-ol increase the survival rate in a hermetic chamber and that this effect is arrested by naloxone, nalorphine, and TRH. Tyr-D-Ala-Gly-D-Leu, an agonist of delta-opiate receptors has no antihypoxic properties. The data obtained point to the involvement of opiate receptors (at least of those of the mu-type) in realization of the reactions that increase the resistance to hypoxia. Bicuculline was shown to be able to remove the antihypoxic effect of the agonists of opiate receptors, suggesting the GABAergic modulation of this effect.

Animals↗
PubMed1984

[Differences in the mechanism of the antihypoxic action of benzodiazepine receptor agonists and muscimol].

Neuropharmacological analysis of previously revealed antihypoxic activity of benzodiazepines (BDZ) has been performed in experiments on mice exposed to hypoxia. Antihypoxic effect of diazepam is shown to be antagonized by the central BDZ receptor blocker, Ro 15-1788. A certain degree of antihypoxic activity also abolished by Ro 15-1788 is exhibited by hypothetical ligands of BDZ receptors: inosin, nicotinamide, ethyl-beta-carboline-3-carboxylate. The effect of dipyridamole, a drug with high affinity for BDZ receptors of the peripheral type is not antagonized by Ro 15-1788, another evidence of Ro 15-1788 affinity precisely to the central BDZ receptors. GABA-mimetics (muscimol and GABA cetyl ester) were also found to have marked antihypoxic activity. Unlike BDZ receptor agonists, this effect is reduced by bicuculline and not by Ro 15-1788. The data obtained suggest that antihypoxic activity of BDZ is caused by their direct interaction with the central BDZ receptors, probably with the type which is not modulated by GABAA receptors.

Animals↗
PubMed1984

[Effect of gamma-aminobutyric and gamma-hydroxybutyric acids on the arousal of susliks from hibernation].

Experiments on male red-cheeked sousliks were made to examine the effects of substances interfering with different stages of GABA shunt on the animals' awakening assessed from the times of formation of the orthostatic reflex, the time course of rectal temperature, and the moment of the occurrence of active movements. The substances reducing (thiosemicarbazide) GABA content and elevating it (amino-oxyacetic acid) in the cerebral tissue have no effect on the above-indicated parameters of awakening. Meanwhile, p-dipropyl acetate (depakin) provokes a distinct dose-dependent increase in the time required for the recovery of the orthostatic reflex and transition to an active state. Sodium gamma-hydroxybutyric acid (GHBA) produces an analogous but more pronounced action. Both the drugs exhibit this effect when given even in low doses, in which they do not inhibit the thermogenesis. This evidence combined with the reported data on high GHBA concentration in brown fat suggests that GHBA may play a specific role in the mechanisms of hibernation.

Aminooxyacetic Acid↗
PubMed1984

[Nootropic properties of gamma-aminobutyric acid derivatives].

Experiments on rats and mice were made to study the antianamnestic and antihypoxic effects of some GABA derivatives. Cetyl GABA, sodium and lithium hydroxybutyrates and phenibut were shown to be able to decrease the retrograde amnesia caused by electroshock in passive avoidance performance. As regards the degree of the antianamnestic effect, the above-mentioned non-cyclic derivatives of GABA are not inferior to the standard nootropic drug piracetam, a derivative of cyclic GABA. Antihypoxic activity of sodium hydroxybutyrate, cetyl GABA, phenibut and lioresal studied in experimental hypoxic hypoxia compares very favourably with that of piracetam. The compounds under consideration manifest their protective action against damaging factors in doses which do not provoke muscle relaxation or any types of central depression. According to the data obtained one may conclude that the nootropic effect is exhibited by not only piracetam, a derivative of cyclic GABA, but also by some of its non-cyclic derivatives.

Amnesia↗
PubMed1982

[Neuropharmacological properties of piracetam derivatives].

Piracetam and its 8 derivatives were studied in experiments on mice and rats with the use of standard neurotropic tests and nootropic activity tools. The electrophysiological index of GABA-ergic inhibition (the recovery cycle of cortical evoked potentials) was also investigated. It was shown that piracetam derivatives as well as piracetam itself have a pronounced antihypoxic activity and prevent the amnestic effect of electroshock in experimental passive avoidance. Most of them were inactive according to the standard neurotropic test. Piracetam derivatives with a hydrazide grouping in the side chain combine nootropic activity and a specific stimulant effect, while the derivatives possessing a phenyl ring combine nootropic and depressant activity.

Amnesia, Retrograde↗
PubMed1982

[Mechanism of antihypoxic effect of depakine].

It was shown that depakine (valproate) increases the lifespan of mice under hypoxic hypoxia, delays the appearance of rhythm disturbances and increases the total duration of ECG maintenance in rats in a low pressure chamber. Depakine was found to reduce the background level of lactate in brain and cardiac tissues and to prevent lactate accumulation characteristic of hypoxia, as well as the shift in its standard ratio with pyruvate. Comparison of depakine with other GABA-ergic compounds with the use of the tests cited revealed that as regards the nature of its protective effect in hypoxia, depakine is close to sodium hydroxybutyrate and succinic semi-aldehyde. By antihypoxic action depakine significantly exceeds piracetam. Analysis of the effects of the inhibitors of various reactions of the "GABA shunt" suggests that the inhibition of succinic semi-aldehyde dehydrogenase accompanied by the enhanced NAD-dependent reduction of succinic semi-aldehyde to gamma-hydroxybutyric acid plays an important part in depakine antihypoxic action.

4-Aminobutyrate Transaminase↗
PubMed1982

[GABA-ergic cortical component in the action of piracetam and cetyl GABA].

The effect of piracetam on the electrophysiological and biochemical characteristics of the GABA system was studied and compared to that of cethyl ether of GABA (CEGABA). It was shown that piracetam (250-500 mg/kg) enhances the test response depression in the primary response recovery cycle and produces synchronization of the ECoG of the sensomotor cortex similarly to the previously described GABA-positive substances. The synchronizing effects of piracetam are retained upon isolation of the cortex and can be removed by bicucullin (rather than by strychnine) applied to the cortex. Piracetam decreases the GABA content in the brain cortex and inhibits the activity of glutamate decarboxylase. Analogous effect is exerted by CEGABA. A conclusion is drawn that GABA-ergic processes get potentiated under the effect of both the drugs. The selectivity of piracetam effects as to the cortical GABA-ergic inhibitory systems is likely to be the reason for the absence in the drug of anticonvulsant effect inherent in GABA mimetics with more generalized effects (CEGABA, muscimol).

Animals↗
PubMed1982

[Effect of prostaglandins, cyclic nucleotides and ions on the analgesic effect of enkephalin analogs].

The effect of intracellular modulators and ions on the analgetic action of the two tetrapeptide analogs, Tyr-D-Ala-Gly-Phe-NH2 and Tyr-D-Ala-Gly-Phe (NO) NH2, was studied in rat experiments. The threshold of pain reaction to electrical stimulation of the tail, evidenced by vocalization, was measured. PGE1, PGE2, PGE2 alpha, cAMP, and dibutyryl cAMP were shown to diminish the effect of the above-mentioned enkephalin analogs. In contrast to cAMP, cGMP was not active in this respect. Among the ions under study (calcium, lithium, rubidium, and cesium), cesium was shown to be the most active. It prevented the increase of the pain reaction threshold and shortened the duration of analgesia. Lithium had no antagonistic effect as regards the enkephalin-induced analgesia. Comparison of these findings with the previously obtained data on the antagonism of the substances under consideration with morphine suggests similarities in the mechanisms of modulation of the effects of opiates and opioids. At the same time the failure of lithium to antagonize the enkephalin analogs and the presence of morphine antagonism point out that the similarities in the mechanisms of ion regulation of exogenous analgetics and enkephalins cannot be regarded as complete enough.

Analgesia↗
PubMed1981

[New evidence for a GABA-ergic component in the mechanism of action of benzodiazepine tranquilizers].

Studies of impulse summation in the rabbit central nervous system have shown that valproate, an agent potentiating GABA-ergic inhibition, reduces while thiosemicarbazide and bicuculline that lower GABA inhibitory effects increase impulse summation. It has been also discovered that the action of phenazepam and diazepam is potentiated by valproate and reduced by thiosemicarbazide and bicuculline. According to the authors' data, diphenylhydantoin, an anticonvulsant having no GABA-positive effect fails to produce selective reduction of impulse summation. The data presented may be regarded as new evidence gained in the whole body for participation of the GABA-ergic mechanisms in the development of benzodiazepine effects.

Animals↗