Biomedical subjects
Publications and source records attributed to V V Zakusov.
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.
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.
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.
The influence of ecgonine, tropine, tropinon, and some of their derivatives, propan, N-methylpyrrholidine, N-methylpiperidine on impulse summation in the central nervous system, conditioned reflex of avoidance, antagonism to hexenal, synergisim to cocaine and also their toxicity (LD50) have been studied under experimental conditions. As shown, benzoyl-ecgonine, ecgonine methyl ester, ecgonine, tropine, pseudotropine, carbomethoxytropinon, tropinon, tropine, tropan N-methylpyrrolidine, and N-methylpiperidine produced a pronounced stimulating effect on the central nervous system activity; in this respect they were similar to cocaine. The following conclusions were made: the substances whose molecules contained tropan structure or one of its fragments possess the central stimulating effect. The stimulating effect of cocaine on the central nervous system could be due to the tropan fragment of its molecule.
Drugs of the benzodiazepine series (clonazepam, lorazepam, diazepam and medazepam) increase the inhibitory processes in the cerebral cortex as it has been shown by means of the recovery cycles of the intracortical response. There is a correlation between the effect on the recovery cycles and their protective action against convulsions induced by GABA deficit. Diazepam enhances the inhibitory effect of GABA applied iontophoretically to rabbit sensorymotor cortex neurons. The drug GABA-ergic effect seems to be specific since it fails to modify the effects of other putative neurotransmitters (glutamate, glycine, acetylcholine). The alteration of rat conflict situation behaviour under diazepam has been eliminated due to the blockade of GABA-receptors by gicuculline and the decrease of the GABA level by thiosemicarbazide. It is inferred that the main effects of benzodiazepines are mediated by GABA and suggested that these agents increase the sensitivity of postsynaptic GABA-ergic receptors.
A selective uptake of ethanol by presenting its 5% solution as the only source of fluid was elaborated in rats for 2 months. It was found that lithium chloride injected intravenously in a dose of 35 mg/kg twice per 24 hours for 14 days depressed the ethanol preference causing a motivation inversion whose mechanism was associated with the changes in the activity of the hypothalamic centres of the neuroendocrine regulation. A possibility of lithium salts in the therapy of chronic alcoholism is discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
Diazepam was shown to increase postexcitatory inhibition within the brain cortex as revealed by its influence upon the recovery cycles both of intracortical and primary responses. The specific interrelationship between diazepam and some drugs affecting brain GABA level suggests the possibility of a GABA mediated mechanism in the diazepam effect. The sensitivity of the brain cortex to diazepam is not lower than that of the amygdala and significantly higher than that of the hippocampus.
Cocaine influence on the central action of noradrenaline was studied in experiments on rabbits by the method of impulse summation. Cocaine was shown to increase the noradrenaline action of the central nervous system. Thus, cocaine intensified not only the peripheral effects of noradrenaline (this was known before), but its central action as well.
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.
Explore the source record for details and available documents.
The depressive action of intravenously injected diazepam on the spontaneous electric activity of the sensomotor cortex neurons was studied in acute tests on rabbits. After introduction of 1 mg/kg of the drug an acute tolerance of a repeat introduction of it in the same dose developing 40--60 min following the first injection was observed. Earlier after the first injection (up to 20--40 min) the tolerance was lacking. It is suggested that the tolerance of a repeat introduction of diazepam is due to a concurrent blocking of the nervous tissue receptors sensitive to diazepam by the products of its (diazepam) metabolism.