[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.

[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.

[Mechanism of action of eserine on DNA synthesis in rat liver]. / K mekhanizmu deistviia ézerina na sintez DNK v pechenii krys.

Eserine (1-2 mg/kg) decreased incorporation of the radioactive precursors into total DNA of the rat liver by 40-50%. Only high eserine cincentrations (10-5 M) effected directly the DNA synthesis in the hepatocyte nuclei. It was shown in vitro that the DNA synthesis in the nuclei of hepatocytes, isolated from the liver of rats after eserine administration (1 mg/kg), decreased significantly. A conclusion is drawn that the eserine action on the incorporation of radioactive precursors into DNA of the rat liver in vivo is localized at the level of the DNA synthesis in the nuclei. The study of the acetylcholine action on the DNA synthesis in the isolated nuclei of hepatocytes suggests that the inhibitory effect of eserine on the DNA synthesis is mediated through acetylcholine.

[Effect of eserine on DNA synthesis in rat liver]. / Vliianie ézerina na sintez DNK v pecheni krysy.

Incorporation of labelled precursors into total and nuclear DNA of liver tissue was inhibited after administration into animals of eserine at a dose 0.1--0.2 mg/100 g of body weight. Simultaneously, DNAase activity was increased and cholinesterase activity was inhibited in liver tissue. The DNA synthesis was inhibited in liver slices, if they were incubated with 2.10(-6) M eserine. The DNAase activity was unaltered in vitro. A cholinolytic compound metacin, pre-administered into the animals, was ineffective at dose of 1 mg/kg; it slightly decreased the effect of eserine at dose of 0.25 mg/kg.