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Biomedical subjects

V V Zakusov

Publications and source records attributed to V V Zakusov.

At least 19 recordsLinked to original sources
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↗
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

[Mediators in the mechanism of the neurotropic action of thyroliberin].

The involvement of acetylcholine (ACH), noradrenaline, gamma-aminobutyric acid (GABA) in the mechanism of neurotropic action of thyrotropin-releasing hormone (TRH) was studied by pharmacological analysis. Spontaneous locomotor activity of mice and antagonism to hexenal according to the awakening effect in mice were used as parameters of the physiologic action of TRH. Agonists and antagonists of appropriate neurotransmitters were employed for pharmacological analysis. TRH appeared to bean antagonist of atropine and physostigmine by locomotor activity and hypnotic effect of hexenal and to be an agonist of phenylephrine, isadrin, amphetamine and an antagonist of phentolamine and propranolol as shown by behavioral tests. According to the same tests TRH was found to be an antagonist of muscimol and an agonist of bicuculline. Thus, it may be assumed that ACH, NA and GABA are involved in TRH mechanism of action.

Animals↗
PubMed1984

[Effect of tropane on the cholinoreceptors of the cerebral cortex].

Spontaneous electric activity of single neurons of the sensorimotor cortex was recorded extracellularly in experiments on unanesthetized rabbits. During microiontophoretic application of tropane and acetylcholine to the neurons, the response to both the agents was the same. The cells excitable by acetylcholine are also excitable by tropane, while those inhibited by acetylcholine are also inhibited by tropane. The cells that do not respond to acetylcholine are also irresponsive to tropane. The excitatory response pattern to tropane is similar to that of acetylcholine. Under the same conditions of microiontophoretic application, tropane causes less excitation as compared with acetylcholine. Tropane preliminarily applied to the neuron reduces the excitatory effect of acetylcholine. The possible role of agonist-antagonist relations between tropane and acetylcholine in the mechanism of the pharmacological effects of tropane and its derivatives is discussed.

Acetylcholine↗
PubMed1983

[Combined action of caffeine and sydnocarb].

Combined application of two stimulants caffeine and sydnocarb (a sydnonimine derivative) was studied in rabbits, rats and mice using the method of summation of impulses in the central nervous system, the method of conditioned avoidance response, forced swimming and hexobarbital sleep in order to find out the changes in their main and side effects. It was established that the main stimulant effect of the drug combination given in optimal doses appeared to be additive, while side effects on the ECG and blood pressure remained unchanged.

Animals↗
PubMed1983

GABA-opiates interactions in the activity of analgesics.

The influence of compounds which reduce or potentiate GABA-ergic inhibition on the effect of analgesics of various structures was studied. The effect was estimated according to the analgesic activity (experiments in rats) and the suppression of the impulse summation in the central nervous system (experiments in rabbits). It was shown that GABA-negative agents (bicucullin, thiosemicarbazide) markedly decreased the effect of morphine, hydrocodone and the enkephaline analogs: Tyr-D-Ala-Gly-Phe-NH2 and Tyr-D-Ala-Gly-Phe(NO2)NH2. The action of bicuculline was close to that of naloxone, an opiate receptor blocker. GABA-positive agents (muscimol, GABA cetyl ether, valproate) potentiated the activity of the mentioned narcotic analgesics. The effect of GABA-positive agents was blocked not only by GABA-negative compounds, but also by naloxone. The obtained data are interpreted in terms of the assumed mutual complementary of GABA-ergic and opioidergic systems. It was shown that the effects of the analgesics of a different structure: phenylpiperidine derivatives (trimeperidine, fentanyl), diphenylacetic acid derivative (dimenoxadol) and 3-benzazocine tricyclic derivative (pentazocine) were unchanged by the studied GABA-ergic analyzers. The reasons for those dissimilarities between analgesics of different structures are discussed.

Aminooxyacetic Acid↗
PubMed1983

[Pharmacology of thyroliberin].

The influence of synthetic thyrotropin-releasing hormone (TRH) on locomotion, on the effects of analgetics, learning and memory, electrical activity of hypothalamic neurons, blood pressure, and cerebral circulation have been studied. TRH increases the spontaneous motility and potentiates the stimulating effect of amphetamine and apomorphine. It also antagonizes the decrease of motility induced by tetrabenazine in all these tests. TRH exhibits the similarity to antidepressants. TRH antagonizes the effects of morphine and Tyr-D-Ala-Gly-Phe-(NO2)-NH2, especially in respect of respiratory depression experiments made on rats and rabbits. TRH facilitates the learning in active avoidance paradigme, diminishes the degree of retrograde amnesia evoked by maximal electroconvulsive shock. The latter effect suggests that TRH can be considered as a substance having some signs of nootropic activity. TRH seems to interact with central M-cholinergic system. This is evidenced by the ability of atropine to diminish the excitatory effect of TRH applied microiontophoretically to single neurons of the lateral hypothalamus. TRH elevates blood pressure and volume velocity of the cerebral circulation in normotensive animals and recovers the hemodynamics during hemorrhagic hypotension. The spectrum and mechanism of TRH pharmacological activity are discussed. The data suggest that TRH may be of interest for clinical trials.

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

[Morphine-like activity of the enkephalin analog Tyr-D-Ala-Gly-Phe-NH2].

The analgetic activity of the tetrapeptide enkephalin analog, its influence on the interneuronal transmission of excitation in various areas of the central nervous system and on opiate receptors of vas deferens were studied. The tetrapeptide was found to have a marked analgetic effect during intravenous injection to mice but to be less active than morphine. The tetrapeptide as well as morphine inhibited the impulse summation in rabbits and both spontaneous and bradykinin-induced neuronal activity in the rat sensory motor cortex. The tetrapeptide inhibited the contractions of isolated vas deferens in mice. The opiate antagonist naloxone eliminated both analgetic effect of the tetrapeptide and its inhibitory effect on the impulse summation, neuronal activity and contractions of vas deferens.

Analgesics↗
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↗
PubMed1981

[Effect of motropin and naloxone on electroacupuncture analgesia].

It was demonstrated in experiments on awake rabbits that electroacupuncture increases the pain threshold (the tail-flick-test) and suppresses the second positive wave of evoked potential in the somatosensory cortex in response to nociceptive electrocutaneous stimulation. Naloxone, the typical antagonist of narcotic analgetics, in doses of 0.05-0.1 mg/kg completely blocks the effects induced by electroacupuncture. The similar effects were produced by motropin, a new antagonist of narcotic analgetics, belonging to the tropan series, administered in doses of 10-20 mg/kg.

Acupuncture Therapy↗