[The pharmacokinetic interaction of cholinolytics and cholinesterase reactivators as a reflection of the modulation of their binding in blood plasma and in brain tissue]. / Farmakokineticheskoe vzaimodeistvie kholinolitikov i reaktivatorov kholinésterazy kak otrazhenie moduliatsii ikh sviazyvaniia v plazme krovi i v tkani mozga.

Radioligand assay showed that the cholinesterase (ChE) reactivators dipiroxime and benzyxime, but not carboxime, modulate selective absorption of some cholinolytics (tributam, pediphen, aprophen) in rat brain. Significant suppression of the specific binding of muscarine antagonists was recorded after chlorophos (2.LD50) intoxication. Under such conditions, the ChE reactivators induce increase in the number of binding sites and in the parameters of the constant of cholinolytic absorption on the brain membranes. It was also established by equilibrium dialysis that the binding of cholinolytics in blood plasma under the effect of ChE reactivators is reduced, leading to redistribution of their free and bound fractures, which is most favorable for tissue sorption.

[The effect of physical loading on the pharmacokinetics of drugs]. / Vliianie fizicheskoi nagruzki na farmakokinetiku nekotorykh lekarstvennykh sredstv.

In model experiments on rats performed with the use of radioindication assay and the HPLG method it was shown that the total level of cholinolytics, pediphen (20 mg/kg) and peniphin (6 mg/kg) reliably decreases in plasma after oral administration during physical exercise (method of free swimming under loading). At the same time the intramuscular injection of pediphen (2 mg/kg) and peniphin (0.6 mg/kg) induce a reliable increase in the concentration of cholinolytics in plasma under the influence of physical exercise. The mechanism of observed changes in pharmacokinetics of neurotropic drugs are discussed. The results of this study may be used in therapy to optimize doses of cholinolytic drugs in conditions of physical and/or locomotor activity.

[The polymorphism of the pharmacological effects of calcium channel blockers]. / Polimorfizm farmakologicheskikh éffektov blokatorov kal'tsievykh kanalov.

In experiments on mice and rats it was shown that the studied calcium channel blockers--verapamil (finoptin, isoptin), nifedipine (corinfar), sensit (phendilin), cinnarizine (stugeron), diltiazem--are heterogeneous by their pharmacological properties. No relationships between the antiarrhythmic, anticonvulsant and cholinolytic effects of the compounds were revealed. It was supposed that the cholinolytic activity of nifedipine and diltiazem in arecoline salivation test reflects not their competitive relations with acetylcholine on the active surface of the receptor, but rather is realized at the level of the signal transmembrane transmission systems.

[Cerebral blood flow function during altered cholinergic mediation]. / Sostoianie mozgovogo krovotoka pri izmenenii kholinergicheskoi mediatsii.

The study of cerebral blood flow was performed with the aid of hydrogen clearance technique and the cinema-television method in alteration of cholinergic transmission by means of phosphorus-organic inhibitors of cholinesterase and a cholinolytic agent in unanesthetized rats. The enzyme inhibition by 60-70% sharply increased the velocity of blood flow in the microvessels of cerebral cortex and in the sagittal sinus. A considerable vasodilation of pial vessels occurred. Atropine administration reduced the velocity of both the cortical and the total blood flow, increasing the lumen of pial vessels in intact animals. Whereas atropine administration against the background of the inhibitors action normalized the blood low velocity with no elimination of the vasodilation of pial arteries. The findings suggest that atropine widely used in poisoning with various inhibitors of cholinesterase, does not normalize the tonus of cerebral vessels.

[Modification of selective adsorption of muscarinic antagonists in cerebral membranes during chlorophos poisoning]. / Modifikatsiia selektivnoi adsorbtsii muskarinovykh antagonistov na membranakh mozga v usloviiakh otravleniia khlorofosom.

Using radioligand assay it was demonstrated that chlorophos intoxication produced inhibiting effect on the kinetics of membrane binding of 3H3-quinuclidinylbenzilate and 14C-cyclosil in the brain. Cholinesterase reactivator dipyroxime was shown to induce normalization of the cyclosyl specific binding kinetics. It seems to be justified to propose that cooperative action of cholinolytic agents and cholinesterase reactivator at the level of m-cholinoreceptors in the course of intoxication may be one of the mechanisms of the potentiation of therapeutic effects of these drugs.

[Pharmacokinetics of dipyroxime in the body of rats and dogs]. / Farmakokinetika dipiroksima v organizme krys i sobak.

Pharmacokinetics of dipyroxime was studied following intravenous injection to noninbred albino male rats. Dipyroxime is a cholinesterase reactivating drug now widely used as an antidote in poisonings caused by organophosphorus pesticides. Dipyroxime pharmacokinetics analysis made it possible to propose a formula for approximation of the data on another animal species (dogs). The drug concentration in the dog blood plasma is in a good correlation with the predicted level.

[Changes in the lesser circulation as affected by armin]. / Izmenenie krovoobrashcheniia v malom kruge pod vliianiem armina.

Experiments on narcotized cats have shown that intravenous administration of armine in DL50 (0.2 mg/kg) decreases the pulmonary blood flow by 52%. The reduction of the pulmonary blood flow is accompanied by a drop of pressure in the femoral artery, development of bronchoconstriction, bradycardia and arterial hypoxemia. The pressure in the lung artery remains rather high. At the beginning of intoxication the decrease of the pulmonary blood flow correlates with bronchoconstriction in a greater degree than with other indicators and as the pathological process deepens, the reduction of the pulmonary blood flow gets closely connected with bradycardia.

[Effect of armin on the microcirculation of the cerebral cortex of white rats]. / Vliianie armina na mikrotsirkuliatsiiu v kore golovnogo mozga belykh krys.

Experiments on white male Wistar rats with the use of the cinetelevision technique have shown that armine in a single LD50 provokes a 85-100% increase in the blood flow rate in the microvessels and a 45-50% elevation of the diameter of the pial arterioles. Administration of the drug in a dose of 1/2 of the LD50 brings about a 90% increase in the blood flow rate, whereas the diameter of the arterioles declines by 25%. The LD50 of armine lowers the cholinesterase activity in the brain and blood by 50-60%, while 1/2 of the drug LD50 by 20-30%.