[The new combined antituberculous drug: the original combined antituberculous drug dioxazid].

The new combined antituberculous drug dioxazid was designed on the basis on the synergism of isoniazid and dioxidine. The dosage form of the drug is a lyophilized powder (containing dioxidine, 100 mg, and isoniazid, 250 mg) in flasks. Its activity and toxicity were tested in an experiment on laboratory animals. Clinical studies were conducted in the treatment of patients with tuberculous empyema (n = 25) and those with endobronchial pathology of tuberculosis and comorbid genesis (n = 30). Dioxazid was ascertained to show a good efficacy. At the same time, the doses of this combined drug, recommended for the treatment of tuberculosis, are much smaller than those of both that are components of the combination, which are used alone. The side effects characteristic for each component are not potentiated when isoniazid and dioxidine are concurrently used in the developed dosage form.

[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.

[Sensitivity of influenza A/H5 viruses isolated from wild birds on the territory of Russia to arbidol in the cultured MDCK cells].

The effect of the antiviral drug arbidol on the reproduction of avian influenza A/H5 viruses was studied in in vitro experiments. The strains were isolated from the wild birds of Eastern Siberia and they were closely related to the 1997-2000 viruses from South-Eastern Asia. Arbidol was shown to exert a selective inhibiting effect on the reproduction of these viruses in the MDCH cell cultures.

Spike activity of neurons in the lateral hypothalamus in rats during microiontophoretic application of melatonin and noradrenaline.

Microiontophoretic application of melatonin to the perineuronal space of nerve cells in the lateral hypothalamus of WAG and Fischer-344 rats led to decreases in the frequency and regularization of the spike activity of neurons, and also blocked activation of neurons and changing the patterns of adrenaline-induced spike activity. The effects of melatonin were more marked in WAG rats, which demonstrated the more active behavior in the open field test and were predicted to be more resistant to emotional stress, than in passive Fischer-344 rats, with predisposition to emotional stress. These results suggest that the mechanism of the stress-protective action of melatonin involves suppression of the spike activity of neurons in emotiogenic brain structures and changes in their sensitivity to noradrenaline.

[Impulse activity of neurons in the lateral hypothalamus during microionophoretic administration of melatonin and noradrenaline in rats]. / Impul'snaia aktivnost' neironov lateral'nogo gipotalamusa u krys pri mikroionoforeticheskom podvedenii melatonina i noradrenalina.

Microionophoretic administration of melatonin into the perineuronal space of lateral hypothalamic neurons in WAG and Fischer-344 rats decreased the firing rate and regularized activity of the cells. Moreover, the effects of melatonin completely blocked the activation of neurons and changes in their pulse activity produced by norepinephrine. The effects of melatonin on neuronal activity in behaviorally active stress-resistant WAG rats were more pronounced than in behaviorally passive stress-predisposed Fischer-344 rats. These data suggest that stress-protective activity of melatonin is associated with inhibition of the pulse activity of neurons in emotiogenic structures of the brain and changes in neuronal sensitivity to norepinephrine.

Synthesis and antifibrillatory activity of nibentan and its analogues.

A series of 1,5-diaminopentane derivatives, structurally related to nibentan, was synthesized and tested for antifibrillatory activity. Improved modifications of some known chemical syntheses were proposed. (+/-)-N-[5-(Diethylamino)-1-(4-nitrophenyl)pentyl]-benzamide hydrochloride, (+/-)-N-[5-(diethylamino)-1-(4-nitrophenyl)pentyl]-4-nitrobenzamide hydrochloride and (+/-)-N-[5-(diethylamino)-1-(4-hydroxyphenyl)pentyl]-4-nitrobenzamide hydrochloride were more potent than nibentan and possessed a longer duration of action (up to 5 h in comparison with 60-90 min for nibentan). The antifibrillatory activity of (+/-)-N-[5-(diethylamino)-1-(4-methoxyphenyl)pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-sotalol and sematilide.

[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.

[The first original Russian class-III antiarrhythmic nibentan]. / Pervyi original'nyi otechestvennyi antiaritmik III klassa nibentan.

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.

[The new antidepressant tetrindole]. / Novyi antidepressant tetrindol.

The antidepressive effects of tetrindole versus pyrazidole (pirlindole) and imipramine were studied in animal experiments. Tetrindole was found to be more active than pyrazidole and imipramine in a behavioral model of Porsolt, in antagonism with reserpine, in potentiation with 5-hydroxytryptophan, L-dopa and clonidine. The action of terindole is related to its ability to exert reversible inhibitory effects on MAO A activity. Tetrindole is less toxic than pyrazidole and imipramine.