[Pharmacology of thyroliberin]. / K farmakologii tiroliberina.

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.

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.

[Effect of motropin and naloxone on electroacupuncture analgesia]. / Vliianie motropina i naloksona na élektroakupunkturnuiu anal'geziiu.

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.

[Mechanism of the central effects of tropane]. / K mekhanismu tsentral'nykh éffektov tropana.

The effect of tropan on exocellular-recorded electrical activity of brain sensorimotor cortical and ventrolateral thalamic neurons was studied in acute experiments on rabbits. Tropan was injected intravenously in a dose of 1-5 mg/kg and applied microiontophoretically to individual neurons. With both routes of administration tropan increased the frequency of spontaneous activity of the majority of cortical and thalamic neurons in the dose-dependent form. The inhibitory action of the microiontophoretically applied catecholamines noradrenaline and dopamine on the activity of brain cortical neurons does not change under the effect of tropan. The stimulatory effect of catecholamines on ventrolateral thalamic neurons is potentiated by tropan. It is suggested that excitation of cortical and subcortical neurons, as well as potentiation of stimulatory catecholaminergic effects in the subcortex underlie the central stimulant effect of tropan.

[Effect of phenazepam on the ethanol demand of rats]. / Vliianie fenazepama na potreblenie étanola krysami.

The new Soviet tranquilizer phenazepam given to rats intraperitoneally at a dose of 1 mg/kg daily was shown to be capable of suppressing ethanol addiction produced by 2-month intake of 5% ethanolic solution as the only source of liquid. The mechanism of this effect is likely to be related to the changes in the activity of the neurosecretory centers of the hypothalamus. The phenazepam in the treatment of chronic alcoholism.

[Pharmacology of azidomorphine]. / K farmakologii azidomorfina.

As revealed, in acute experiments on rabbits, cats, and rats, a new morphine-like synthetic analgesic drug azidomorphine exceeded 20--100-fold the morphine ability to inhibit synaptic transmission in the thalamic structures, cerebral cortex, and the spinal cord during the nociceptive stimulation, and also by its analgesic activity.

[Preventive effect of lithium chloride on the development in rats of a preference for ethanol]. / Preventivnyi éffekt khlorida litiia na razvitie u krys predpochteniia k étanolu.

It was revealed in experiments on rats treated with a 5% ethanol solution with equal quantities of LiCl (experiment) and NaCl (control) for seven weeks as the only source of liquid that with li+ concentration in the blood plasma of approximately 0.6 meq/1 LiCl prevented the development of alcohol dependence. On studying the neurosecretory hypothalamic nuclei, hypophysis and adrenal cortex of the same animals a certain correlation has been demonstrated between the morphofunctional condition of the mentioned formations, the degree of ethanol preference development and the character of LiCl influence on the process.

[Effect of cocaine on the tyrosine hydroxylase of rat hypothalamus]. / Vliianie kokaina na tirozingidroksilazu gipotalamusa krys

The influence of cocaine on tyrosine hydroxilase of rat brain hypothalamus was investigated in vivo (0.5 mg/kg) and in vitro (10(--6)--10(--5)M). Cocaine was used as a substance with a known adrenergic type of action. It was shown that under standard conditions cocaine in vitro increased the enzyme activity and decreased the Km for DMPH4 cofactor without changing Vmax of the reaction analyzed by the membrane enzyme. Cocaine in vitro decreased the tyrosine hydroxylase activity, especially that of the membrane enzyme. In this case there occurred a decrease of Km for DMPH4 and a decrease of Vmax of the reaction. The decrease of Vmax is considered to be the result of the secondary effect of cocaine.

[Effect of several tropane derivatives on noradrenaline absorption by hypothalamic synaptic vesicles]. / Vliianie nekotorykh proizvodnykh tropana na pogloschchenie noradrenalina sinapticheskimi puzyr'kami gipotalamusa

The influence of some tropan derivatives on the absorption of exogenous norepinephrine was studied in experiments on the isolated synaptic vesicles of the hypothalamus. LK II (beta-morpholinopropionic acid tropine ester dihydrochloride) at the concentration of 1. -5M decreased (like cocaine) the passive consumption of norephinephrine. The dependence of this effect on the transmitter concentration in the incubation medium was demonstrated.

[Intracellular mechanism of the action of imipramine and diazepam]. / O vnutrikletochnom mekhanizme deistviia imipramina i diazepama

The content of noradrenaline during the action of antidepressant imipramine and a tranquilizer diazepam was determined in rats by differential centrifugation of the hypothalamus tissues. Imipramine was found to decrease the noradrenaline content in synaptosomes, whereas diazepam failed to evoke any similar effects. Thus, in the action mechanism of the first substance the adrenergic compound was of definite importance, while in the mechanism of the second one it took no part.