[Sensitivity of various influenza virus strains to arbidol. Influence of arbidol combination with different antiviral drugs on reproduction of influenza virus A].

AIM: To study antiviral activity of arbidol in relation to various antigenic subtypes of influenza virus isolated from humans; efficacy of arbidol action in combination with adamantanic antiviral drugs, ribavirin and ribamidil on reproduction of influenza virus A (IVA) in cell culture. MATERIAL AND METHODS: The activity of the drugs against viral reproduction was assessed by inhibition of viral antigens expression detected in virus-infected cells using enzyme immunoassay (EIA). RESULTS: Arbidol is not inferior to adamantanic drugs, neuraminidase inhibitors, ribavirin and ribamidil by its inhibiting activity in relation to influenza viruses A and B. Arbidol inhibits reproduction of human IVA antigenic strains H1N1, H2N2, H3N2 and remantadin-sensitive and remantadin-resistant strains of influenza virus. Arbidol inhibits reproduction of pathogenic for humans strains of avian influenza virus H5N1 and H9N2, strains H6N1 and H9N2 having internal genes common with H5N1 and H9N2. The inhibiting activity of arbidolin on cell culture viral reproduction enhanced if arbidol was used in combination with amantadine, remantadin, ribavirin and ribamidil. CONCLUSION: Arbidol has a wide spectrum antiviral activity and inhibits reproduction of various antigenic subtypes and remantadin-resistent human IVA, avian viruses H5N1 and H9N2, influenza viruses B and C.

[Study of the effect of antiviral drugs on the reproduction of the respiratory syncytial virus by enzyme immunoassay]. / Ispol'zovanie immunofermentnogo analiza dlia izucheniia deistviia protivovirusnykh preparatov na reproduktsiiu respiratorno-sintsitial'nogo virusa.

A test system based on EIA was developed for evaluating the efficiency of drugs active towards the respiratory syncytial virus (RSV) in cell culture. Virasole and its structural analog ribamedii active towards RSV infection and arbidol whose activity in RSV infection is unknown were tested. Like virasole and ribamedil, arbidol inhibited the expression of RSV antigens, the inhibitory effect increasing with the drug concentration and decreased with increase of the multiplicity of virus infection. MIC50 for arbidol, virasole, and ribamedil were 10, 5, and 6 micrograms/ml, respectively. These data prompt clinical trials of arbidol in RSV infection.

[Antioxidant properties of arbidol and its structural analogs]. / Antioksidantnye svoistva arbidola i ego strukturnykh analogov.

The effect of arbidol and its structural analogues on the process of lipid peroxidation in phospholipid liposomes induced by Fe2+ has been investigated. It was shown that the antioxidant efficacy of arbidol and its derivatives is lower than that of alpha-tocopherol by two or three times. It was suggested that the mechanism antioxidant action of the arbidol and its structural analogues consists of scavenging of lipid radicals rather than chelating of Fe2+.

[Mechanisms of arbidole's immunomodulating action]. / Mekhanizmy immunomoduliruiushchego deistviia arbidola.

The immunomodulating activity of arbidole was studied in cultured cells, animals, and human beings. Arbidole was shown to have effects on nonspecific defense factors, on its capacity to induce interferon and activate phagocytes in particular. Arbidole-treated patients with lower baseline immunity showed improvement in immunological parameters (in the counts of CD4 and CD8 lymphocytes, B lymphocytes, in the levels of serum immunoglobulins). Arbidol produces a high preventive and therapeutical effects in influenza A and B and other acute respiratory viral infections, prevents postinfluenza complications, reduces the incidence of exacerbations of chronic diseases in postinfluenza patients. In influenza, the therapeutical efficiency of the drug appears as decreases in intoxication, the severity of catarrhal syndrome, shorter fever and disease in general. Arbidole is beneficial for patients with second immunodeficiency, in those with recurrent herpes infection or chronic bronchitis. After arbidole treatment regimen, postoperative immunological parameters became normal in cardiac surgical patients, which suggests that the drug should be used in cardiac surgical care. The agent showed no side effects in any case.

[Proxodolol pharmacokinetics in rats and rabbits]. / Farmakokinetika proksodolola u krys i krolikov.

In non-inbred rats, the pharmacokinetics of proxodolol was studied after its intravenous administration in a dose of 1 mg/kg or oral use in a dose of 50 mg/kg as 1% aqueous solution, in Chinchilla rabbits, it was examined after intravenous administration in a dose of 1 mg/kg as 1% aqueous solution and oral use in a dose of 40-50 mg/kg as 40-mg tablets. The equilibrium dialysis method was applied to explore proxodolol binding to human and rat serum proteins in vitro. Proxodolol was demonstrated to be slightly distributed in the rat peripheral tissues and more actively in the rabbits (the stationary distribution volume was 0.264 and 2.27 1/kg, respectively). After intravenous injection, the total proxodolol clearance in the rats and the rabbits was 0.229 and 2.24 1/h/kg, the area beneath the concentration-time curve was 5702 and 964 ng/h/ml, the terminal half-life was 1.44 and 1.49 h, the mean retention time was 1.16 and 1.52 h, respectively. The pattern of rabbit serum proxodolol concentration curves after intravenous infusion suggests that the drug shows enterohepatic recirculation. After oral administration, the drug was rapidly absorbed from the gastrointestinal tract; the maximum concentration time was 0.58 h in rats and 0.70 h in rabbits. The mean absorption time was 0.77 and 0.64 h in rats and in rabbits, respectively. The absolute proxodolol bioavailability was determined to be 3.51 and 3.02% in rats and in rabbits, respectively. The in vitro serum protein-binding of proxodolol was 34% in rats and 66% in man.

[Distribution of prazosin and its metabolites in animal organs during chronic administration]. / Raspredelenie prazozina i ego metabolitov v organakh zhivotnykh pri khronicheskom vvedenii.

The distribution of prazosin and its metabolites in organs of rabbits and rats during oral long-term administration at different doses was studied. Prazosin was shown to be accumulated in the animals' organs. Three metabolites of prazosin one of which was identified were detected in the blood serum, bile and organs of the animals. The contents of prazosin and the metabolites in organs and tissues were non-linearly related to the dose.

[Slow elimination of a prazosin metabolite compared to prazosin kinetics after its intravenous administration to rabbits]. / Zamedlennaia éliminatsiia metabolita prazozina v sravnenii s kinetikoi prazozina posle vnutrivennogo vvedeniia krolikam.

Serum concentration profiles of prazosin and its metabolite 2-(1-piperazinyl)-4-amine-6,7-dimethoxyquinazoline after intravenous bolus administration to rabbits (0.5 mg/kg) were shown to be biphasic. Rapid decline related to distribution was followed by a terminal slope lasting for up to 24 hours. Prazosin level in this phase decreased, its elimination half-life being about 9 hours, while the metabolite serum level was almost constant between 4 and 24 hours and averaged 0.9 mumol/l. This is in keeping with the earlier suggested extremely low elimination rate of this metabolite. Enterohepatic recirculation may account for this phenomenon, as well as a significant rise in the metabolite serum concentration I hour after the injection.

[Inhibiting effect of dioxidine on corticosteroid secretion in an experiment]. / Ingibiruiushchee vliianie dioksidina na sekretsiiu kortikosteroidov v éksperimente.

The determination of corticosterone and aldosterone levels in the peripheral blood of rats and a cortisol level in the blood of guinea pigs by a radioimmunoassay following the administration of dioxydin (1,4-N-oxide 2 2,3-dioxymethylquinoxaline) has shown that it produces an inhibiting effect upon the secretion of corticosteroid hormones in animals with a diverse direction of their biosynthesis. There is a dose dependence of the effect detected. Substitution therapy with corticosteroids cuts short adrenal insufficiency caused by dioxydin.

[Toxicological study of the Soviet tetracyclic antidepressant inkazan]. / Toksikologicheskoe izuchenie otechestvennogo tetratsiklicheskogo antidepressanta inkazana.

The toxicology of an original Soviet antidepressant inkasan-3-methyl-8-methoxy-3H, 1,2,5,6-tetrahydropyrazino [1,2,3-ab] beta-carboline hydrochloride was studied in different types of experimental animals (mice, rats, rabbits, dogs). It was established that the drug is less toxic than imipramine. The toxic manifestations (seizures, stereotypy) seen in dogs receiving high doses of inkasan for a long time are likely to be linked with a stimulating component that characterizes the drug action on the central nervous system.

[Tolerance for nonsteroidal anti-inflammatory agents by experimental animals during pregnancy]. / Perenosimost' nekotorykh nesteroidnykh protivovospalitel'nykh sredstv éksperimental'nymi zhivotnymi pri beremennosti.

The authors studied the tolerance of three nonsteroidal anti-inflammatory drugs, voltaren, indomethacin and ibuprofen by rats at different times of pregnancy and compared voltaren tolerance by pregnant and nonpregnant females. It was shown that as compared to nonpregnant animals, pregnant animals tolerated voltaren more poorly. The tolerance of both voltaren and indomethacin was particularly poor in the last trimester of pregnancy. The enhancement of the drug toxicity during pregnancy because of the changes in body function is discussed.

[Circadian fluctuations in dioxidine toxicity]. / Sutochnye kolebaniia toksichnosti dioksidina.

It has been established in rat experiments that toxicity of the antibacterial drug dioxydin (1,4-di-N-oxide 2,3-dioxymethylquinoxaline) depends on the time of administration. The drug exhibits the minimal and maximal toxicity upon administration at 8 o'clock p.m. and at 12 o'clock, respectively.

[Effect of phenobarbital, hexamidine and benzonal on the toxicity of dioxidine]. / Vliianie fenobarbitala, geksamidina i benzonala na toksichnost' dioksidina.

It has been shown in experiments on rats that phenobarbital, hexamidine and benzonal administered in doses producing the induction of liver microsomal enzymes reduce the total toxic action of dioxydin and pathological alterations in the adrenals induced by dioxydin. A possible mechanism of the effect under consideration is discussed.

[Identification of N,N-dimethyl-O-(beta-D-glucopyranuronosyl)-5- hydroxytryptamine as a bufotenine metabolite in the rabbit]. / Identifikatsiia N,N-dimetil-O-(beta-D-gliukopiranuronozil)-5- oksitriptamina kak metabolita bufotenina v organizme krolikov.

A bufotenine metabolite has been isolated from the rabbit urine by the column chromatography on cellulose and preparative paper electrophoresis in acidic buffer. It has the structure of N,N-dimethyl-O-(beta-D-glucopyranuronosyl)-5-hydroxytryptamine as proved by comparison of chromatographic, electrophoretic and NMR data with those for respective synthetic O-glucuronide.

[Comparative study of dioxidine and quinoxidine in a chronic toxicology experiment]. / Sravnitel'noe izuchenie dioksidina i khinoksidina v khronicheskom toksikologicheskom éksperimente.

The toxicity of dioxydin and quinoxidine was studied in experiments on rats and mice given the drugs intravenously. The target organs for both drugs are the adrenals. The pathological process develops in their cortical layer and continues progressing after the drugs are discontinued. Quinoxidine appeared less toxic owing to which the pathological signs in the adrenals were reversible in the majority of animals given this drug in a dose of 100 mg/kg.

[Role of the adrenals in the detoxication of dioxidine]. / Rol' nadpochechnikov v detoksikatsii dioksidina.

An original antibacterial drug dioxidine was subjected to toxicological studies during long-term parenteral administration of 0.5% solution to rats and guinea-pigs (in doses of 25-100 mg/kg). It was found that susceptibility to the drug correlated well with adrenal function. Guinea-pigs were more susceptible to dioxidine than rats. The data obtained indicate the existence of the interplay between non-specific resistance to toxic agents and glucocorticoid potency.