Biomedical subjects
Publications and source records attributed to S S Krylov.
Pyrroxand and butyroxan -- original drugs possessing hyghly selective alpha-adreno-blocking action at peripheral and central level-relieve symptoms of abstinence syndrome caused by narcotics and other addicting drugs. On the basis of these data it is suggested that adrenergic structures of the brain play a key role in eliciting the abstinence syndrome.
A study was made of the activity of Na, K-ATP-ase and the Na+ and K+ content in the brain of rats with the action of arecoline and amizyl. Both arecoline and amizyl increased the Na, K-ATP-ase activity. This could be associated with the changes in the redistribution of the Na+ and K+ ions in the nerve cell. Arecoline proved to cause changes in the electrolyte distribution by the depolarization type, whereas amizyl--by the type of hyperpolarization of the nerve cell membrane.
The effect of benactyzine (the central cholinolytic) in a dose of 40 mg/kg and arecoline (cholinomimetic) in a dose of 2.5 mg/kg on the activity of Mg2+-dependent ATP-ase and the content of Ca2+ and Mg2+ ions in the brain was studied in rats. It was shown that benactyzine and arecoline evoked a biphasic change in the activity of the enzyme and the electrolyte content. A conclusion was drawn that the enzyme inhibition was connected with the accumulation of Ca2+ ions in the brain tissue, whereas its inhibition--with the Mg2+ ion accumulation. It is supposed that throught these effects benactyzine and arecoline influenced the release and retention of the neuromediators in the tissue depot.
The effect of norepinephine, an adrenomietic drug, and of pyrroxane, its antagonist, on diethylnitrosoamine (DENA) hepatocarcinogenesis was studied in albino rats. Norepinephrine was found to stimulate carcinogenesis, whereas pyrroxane--to inhibit this process; the latter drug decreased the incidence of multicentric tumours of the liver. In vitro experiments on the isolated rat atria showed low DENA concentrations (1x10(-6) to 1x10(-8) M) to sensitize the atrium adrenoreceptors to the endogenous and exogenous norepinephrine. A new hypothesis on the adrenergic component in the DENA carcinogenic effect caused by the endogenous norepinephrine is presented.
The distribution of adrenoblocking drug pyrroxan in the blood plasma and different organs of albino rats had been studied. A rapid appearance of pyrroxan in the brain liver, kidneys, and other organs was shown; its selective accumulation in the hypothalamus was found. As revealed spectrofluorimetrically unchanged pyrroxan molecules disappeared from the plasma and the organs within 2 hours. When pyrroxan-14C was used the radioactivity in the organs was demonstrated for 24 hours, and in the plasma for several days; this indicated the formation of pyrroxan metabolites or its complexes with the plasma proteins and structural elements of the organs. The selective accumulation of pyrroxan in the hypothalamus can account for the high efficacy of this drug in different hypothalamic disorders coursing with the overexcitation of the sympathetic nervous system.
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The influence of M-cholinolytics (amizyl, glipine, cyclozyl and 4-oxypiperidylbenzylate) in 0.01--10 mg/kg doses on EEG and photic driving in structures of the visual analyser was studied in experiments on twenty intact rabbits with chronically implanted electrodes in the optic chiasm, the optic tract, the lateral geniculate body and the visual cortex. All M-cholinolitics in the doses studied produced synchronization of the EEG. Photic stimulation against the background of small doses of M-cholinolytics (0.01--0.5 mg/kg) did not lead to any disturbances of photic driving. With increased doses of cholinolitics up to 1--5 mg/kg only low frequencies (1--5 imp/sec) produced driving in the lateral geniculate body and the visual cortex, while in the optic tract the driving remained at the initial level. Administration of drugs in a 10 mg/kg dose resulted in complete depression of the driving response in the lateral geniculate body and visual cortex, while in the optic tract the driving was retained.
Amisyle and arecoline were found to be antagonistic drugs in the effect on content of Mg2+ and Ca2+ and on activity of corresponding ATPases in synaptosomes isolated from rat brain. Amisyle promoted the incorporation of 45Ca into synaptosomes but arecoline inhibited the reaction. The appear to be responsible for liberation and maintaining of neurotransmitters in presinaptic stores.
It has been shown that there are some significant differences in behavioural effects of exogenous thyroliberin for different mammals (mice, rats, dogs, monkeys). The necessity of a careful preclinical trial of peptide drugs is discussed.
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