[Anti-arrhythmia activity of crown-lactone I and its effect on aconitine-modified sodium channels]. / Antiaritmicheskaia aktivnost' kraun-laktona I i ego deistvie na modifitsirovannye akonitinom natrievye kanaly.

Antiarrhythmic activity of macrocyclic crown-lactone I as well as its effect on biological and model membranes were studied. Crown-lactone displaces the potential dependence of stationary inactivation of TTX-sensible sodium neurons currents towards more negative potentials reducing the modification of those characteristics by aconitine. Proceeding from the comparison between crown-lactone and known antiarrhythmic agents effect on sodium currents a conclusion is made that crown-ethers antiarrhythmic activity cannot be explained by the rhythmoinotropic effect.

[Effect of tilorone on the immunological indices of guinea pigs with synestrol-induced glandular hyperplasia of the endometrium]. / Vliianie tilorona na nekotorye immunologicheskie pokazateli u morskikh svinok s zhelezistoi giperplaziei éndometriia, indutsirovannoi sinéstrolom.

The immune system state was studied before and after administration of tilorone (an immunologic adjuvant) to guinea pigs with synestrol-induced glandular hyperplasia of endometrium. The total amount of T- and B-lymphocytes. T-lymphocytes with receptors to the Fc-fragment of IgM and IgG, the content of immune complexes were determined. Immune and nonimmune adherence of neutrophils was investigated as well. It was established that the total amount of T-lymphocytes decreased and the quantity of T-lymphocytes and immune complexes increased with the development of glandular hyperplasia of the endometrium. The tilorone administration normalized the structure of endometrium and T-lymphocyte immune controlling system.

[Search for and study of antiarrhythmic substances among crown ethers]. / Poisk i izuchenie antiaritmicheskikh veshchestv v riadu kraun-éfirov.

The authors studied antiarrhythmic properties of macrocyclic polyesters. Some of the esters exhibited antiarrhythmic activity coupled with low toxicity. It was found that antiarrhythmic action of these substances is not mediated via acetylcholine and/or catecholamine system responsible for nervous regulation of the cardiac activity. The compounds under study were found to have marked antifibrillar properties. Experiments on an isolated rat heart demonstrated calcium specificity of the antifibrillar action of cyclolactones. It is assumed that macrocyclic polyesters represent a new class of antiarrhythmic agents having a direct cardiotropic action.

[Effect of the macrocyclic polyether 15-crown-5 on the ionic permeability of excitable membranes]. / Vliianie makrotsiklicheskogo poliéfira 15-kraun-5 na ionnuiu pronitsaemost' vozbudimykh membran.

The macrocyclic polyether 15-crown-5 at a concentration of 5 . 10(-5)-10(-3) M reduced the frequency of the contractions of an isolated rat auricle, increasing the refractory period of the contractions. The polyether lowered the rate of activation of the slow input current of rat spinal ganglionic neurons and blocked the sodium channels of the electroexcitable membrane without disturbing the function of activation and inactivation mechanisms. The compound under study considerably delayed the onset of and decelerated reactivation of the sodium input current. These actions were calcium-dependent, becoming more demonstrable with reduction of Ca2+ concentration outside the cell. 15-Crown-5 interfered with the action of Ca2+ on the lipid bilayer membrane potential. It is assumed that all the effects described are determined by the formation of 15-crown-5-Ca2+ complexes, thereby leading to the impairment of the packing of the membrane lipoprotein matrix.

[Spectral changes in the liver microsomal cytochrome P-450 of rats during interaction with phenazepam and its 3-hydroxy metabolite]. / Spektral'nye izmeneniia tsitokhroma P-450 mikrosom pecheni krys pri ego vzaimodeistvii s fenazepamom i 3-oksimetabolitom.

Phenazepam (I) and 3-hydroxymetabolite (II) interacting with cytochrome P-450 of the liver of rats administered phenobarbital and 3-methylcholantrene demonstrated the 2nd type of spectral changes in hemoprotein. The binding constants of I and II considerably differ, which points to the possibility of interaction of substrates with different areas of hemoproteins. The characteristic points (maximum, minimum, isobestic) of the cytochrome P-450 spectrum were displaced during II titration to the longwave region as compared with I. The calculation of electron density on the atoms of the heterocycle and aromatic nuclei of the molecules of I and II has shown that the differences in the spectra of I and II binding with cytochrome P-450 are determined by the distribution of electron density of their heterocycle.

[Benzo(a)pyrene hydroxylase activity of immunocompetent cells]. / Benz(a)pirengidroksilaznaia aktivnost' immunokompetentnykh kletok.

A study was made of aryl hydrocarbon hydroxylase activity in immunocompetent cells of varying origin and in hepatocytes from CBA mice. The cells from intact animals may be arranged in the following way with regard to the activity of the enzyme: macrophages greater than hepatocytes much greater than thymocytes greater than splenocytes. The immunostimulants (tilorone and its analogs) altered benzo(a)pyrene hydroxylase activity depending on the cell type.

[Effect of polymethylene- and polyhydroxyethylene-bis-(2-amino-1,3-diazepinium) iodides on cell and model membranes]. / Vliianie polimetilen- i polioksiétilen-bis(2-amino-1,3--diazepinii)-iodidov na kletochnye i model'nye membrany.

The effect of polymethylene- and polyoxyethylene-bis-(2-amino-1, 3-diazepinium) iodides on the membranes of neuromuscular synapsis and mitochondria as on the artificial membranes was studied. The compounds examined were shown to change the amplitude and kinetics of postsynaptic membrane responses to acetylcholine. Inhibition of end plate potentials and oxidative phosphorylation of mitochondria with different derivatives of diazepinium correlated with changes in the surface potential of the artificial phospholipid membrane. It is concluded that the derivatives of diazepinium directly interact with ionic channels of the acetylcholine-activated postsynaptic membrane.

[Effect of macrocyclic amidoesters on membranes]. / Vliianie makrotsiklicheskikh amidoéfirov na membrany.

A comparative analysis of new macrocyclic amidoesters effect on the bimolecular lipid membrane as well as on the electroexcitable membrane of snail isolated neurons was carried out. It was shown that the investigated complexes inducing a small change in lipid bilayer conductivity and some changes in Na-Ca neuron current characteristics produce essential changes of rapid potassium as well as late potassium current properties. It was concluded on the basis of these results and potassium compounds specificity that the investigated complexes interact directly with neuron potassium channels.

[Physiological activity of polymethylene and polyoxyethylene bis-(2-amino-1,3-diazepiniuim) iodides]. / Fiziologicheskaia aktivnost' polimetilen- o pilioksiétilen-bis- -(2-amino-1,3-diazepinii)iodidov.

A study was made of physiological activity of a series of new bisquaternary compounds in which the role of cation heads is played by the residues of 2-amino-1,3-diazepinium. Studies performed on a frog neuromuscular preparation showed that the compounds under test effectively block the responses of the postsynaptic membrane to acetylchinoline. The derivatives of diazepinium have pronounced hypotensive and ganglion-blocking properties. Octamethylene-bis-(2-amino-1,3-diazepinium) iodide that appeared to be the most effective of the compounds under test compares very favourably with benzohexonium. It was found to be 1.5 times more powerful as regards the ganglion-blocking and hypotensive activity.

[Dispersion analysis used for assessing the anticonvulsant activity of 1,4-benzodiazepines]. / Ispol'zovanie dispersionnogo analiza dlia otsenki protivosudorozhnoi aktivnosti 1,4-benzodiazepinov.

A study was made of the time course of alterations in the convulsant activity of corazol after injection to mice of 1,4-benzodiazepine derivatives with different chemical structure. Significant anticonvulsant effect of benzodiazepines was observed for 5--120 minutes and was regarded a dynamic index. The maximal action of the drugs was observed within 15--30 minutes. The most pronounced anticonvulsant action was recorded after administering phenazepam and its 3-hydroxyderivative. The dependence of the anticonvulsant effect on the time of experiment and structure of the test compounds was examined by single-factor analysis of variance. The results demonstrate the relationship of differences in the anticonvulsant effects to the time factor and differences in the structure of the test compounds.

[Effect of macrocyclic esters on mitochondrial and phosphatidylcholine membranes]. / Vliianie makrotsiklicheskikh slozhnykh efirov na mitokhondrial'nye i fosfatidilkholinovye membrany.

It has been found that some macrocyclic esters have no ionophoric properties, but can block valinomycin-induced potassium transport in mitochondrial membranes and lessen the potassium current induced by valinomycin in phosphatidylcholine bilayers. It has been also discovered that 36-member cyclic esters of succinic acid and propylene glycoles decrease fluorescence of puridine nucleotides in mitochondria and produce a modifying effect on bimolecular phosphatidylcholine membranes in the medium of litium, calcium and magnesium chlorides at unilateral injection. The results obtained suggest that cyclopolyesters under investigation form mixed complexes with the macromolecules in the composition of mitochondrial and phosphatidylcholine membranes with the participation of the integrated ion.

[Changes in the enzymic activity of monooxygenase components of rat hepatocytes after administration of tilorone]. / Izmenenie fermentativnoi aktivnosti komponentov monooksigenaz gepatotsitov krys pri vvedenii tilorona.

It is established that tilorone-hydrochloride, the antiviral agent, stimulating the interferon synthesis in the organism of animals under experiment inhibits monooxygenase reactions in the albino rat hepatocytes being administered in combination with phenobarbital and 20-methylcholanthrene. The tilorone effect on the N- and O-demethylase activity of the liver microsomes in vitro was studied. It is established that the rate of dimethylaniline N-demethylation and anisole O-demethylation in this case lowers considerably, the character of the kinetic curves being unchanged.

[Nature of the relation between the anticonvulsant action of phenazepam and its concentration in mouse brain]. / Kharakter vzaimosviazi mezhdu protivosudorozhnym deistviem fenazepama i ego soderzhaniem v golovnom mozge myshei.

A method has been suggested for simultaneous recording of the content of 12C-phenazepam and its metabolites in the mouse brain and of minimum effective doses of corasole intravenously that induce the tonic extension of the animals. Parameters of the two-compartmental kinetic model of absorption, distribution and elimination of 14C-products in the mouse brain were determined. These processes conform to the first order kinetics. A correlation was disclosed between the content of radioactive products in the animals' brain and minimum effective doses of corasole. A linear decline of the anticonvulsant action of phenazepam was revealed during the experimental period. Radiochromatography enabled one to detect the parent compound and its 3-hydroxy metabolite in mouse brain extracts.

[Hydroxylation of the aromatic nuclei and heterocyclic ring of the fenazepam molecule in the endoplasmic reticulum of white rats and mice]. / Gidroksilirovanie aromaticheskikh iader i geterokol'tsa molekuly fenazepama v éndoplazmaticheskom retikulume belykh krys i myshei.

The reactions of 14C- and 3H-phenazepam hydroxylation by liver microsomes of mice and rats were examined to detect the formation of 3-hydroxymetabolite and products of aromatic hydroxylation of phenazepam molecule. The kinetics of the appearance of these products was studied. It was established that enzyme complex of mouse microsomes rather produced 3C-hydroxylation of the drug, while microsomes of rats produced reactions of hydroxylation of phenazepam aromatic rings.

[Immobilization of pectawamorine G10x on silichromes]. / Immobilizatsiia pektavamorina G10x na silokhromakh.

Immobilization of pectawamorine G10x on silochromes, using cyanuric chloride, 2,4-toluylene diisocyanate, glutaric dialdehyde, thionyl chloride, phosphorus tribromide, titanium tetrachloride, zirconium oxychloride and hafnium oxychloride was studied. The use of glutaric dialdehyde assured the strongest binding and the preatest stability of activity. Properties of the native pectawamorine G10x and immobilized preparations were studied on a comparative basis. Pectawamorine G10x immobilized by means of hafnium oxychloride showed increased stability when stored at 5 degrees C and used repeatedly. In every case, except for cyanuric chloride and glutaric dialdehyde, maximum activity was at a temperature 10 degrees C higher than for the native enzyme, and optimum pH varied for the preparations with different binding reagents.

[Intrahepatic circulation of 14C-phenazepam and its metabolites in albino rats]. / Vnutripechenochnaia tsirkuliatsiia 14-B-fenazepama i ego metabolitov v organizme belykh krys.

Excretion of phenazepam and its metabolites into the bile and their intrahepatic circulation were studied in experiments on rats, bile donors, who were preliminarily injected 14C-phenazepam (14 mg/kg) intravenously and on recipients who were administered the donor's bile intraduodenally. It was shown that phenazepam (compound I) and its 3-hydroxymetabolite (compound III) are excreted into the bile of the animals. Hydroxyl derivatives are excreted with the bile as glucuronides. Compounds I and III and glucuronide III undergo intrahepatic circulation.