[The first original Russian class-III antiarrhythmic 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 creation of original Russian beta-adrenoblockers].

Results of search for new beta-adrenoreceptor blocking agents of different effects are summarized. Derivatives of 4-hydroxyindolyl-3-acetic acid are characterized by a prolonged beta-adrenoblocking effect, cardioselective beta-adrenoblockers were found among derivatives of N,N-bis(2-hydroxy-3-phenoxypropanol)amine, and highly effective "hybrid" beta-,a-adrenoblockers were detected among derivatives of 3(5)-phenoxymethylisoxazolines and 5-phenoxymethyl-1,2,4,-oxadiasoles. Clinical studies of one of the most promising compounds of the latter series named proxodolol showed it to be a highly effective antihypertensive, antianginal, and antiglaucoma drug.

[A comparative pharmacological study of the serotoninergic antidepressants tetrindole and fluoxetin].

Tetrindol, a selective inhibitor of MAOA (predominantly of serotonin oxidase) and fluoxetine, an inhibitor of serotonin neuronal uptake, were studied in psychotropic tests on mice and rats. Both drugs significantly intensified 5-hydroxytriptophan-induced head twitching, reduced the effect of reserpine and the destructive action of maximal electroshock and the scopalamine-induced transient disruption of memory in a test for conditioned response of passive avoidance in rats and mice. In a behavioral swimming test the drugs were less active.

[Proxodolol, a new domestic preparation for lowering intraocular pressure in glaucoma].

Effects of a Russian b-a-adrenoblocker proxodolol on the intraocular pressure, ocular hemodynamics, pupil diameter, ocular functions, arterial pressure, and heart rate were studied in 105 patients (163 eyes) with primary open-angle glaucoma. A manifest hypotensive effect of proxodolol was due to depression of aqueous humor production and improvement of its outflow. Comparative study of the efficacies of proxodolol and timolol maleate by the blind test and randomization demonstrated the identity of these drugs.

[An experimental study of the antisecretory and antiulcer activities of kviditen].

Quiditene-(qunuclidyl-3)-di-(thyenel-2)carbinole hydrochloride was studied by using various experimental models. The agent was compared with H2-blockers. When gastrically used, quiditene in doses of 5-50 mg/kg dose-dependently decreased gastric acid secretion and prevented acute gastric mucosal lesions.

[Proxodolol--a new beta- and alpha-adrenoblockader].

The beta- and alpha-adrenoceptor blocking activity, the specificity of its beta-adrenoceptor blocking action, partial agonistic and membrane-stabilizing properties, as well as antihypertensive, antiarrhythmic, and anti-ischemic effects were studied. Proxodolol was shown to be superior to labetalol in its beta-adrenoceptor blocking action and similar to it in its alpha-adrenoceptor blocking agent. The drug has no a partial agonistic activity and produces a moderate membrane-stabilizing action.

[A search for new beta-adrenoblockaders in the series of 5-phenoxymethyl-1,2,4-oxadiazole derivatives].

The experiments on anesthesized rats have revealed that some derivatives of (3-amino-2-hydroxypropoxy)phenomethyl-1,2,4-oxadiazole with the oxadiazole cycle at the o-position of the aromatic ring possess a significant beta-adrenoceptor blocking activity associated with alpha-adrenoceptor blocking properties. The most potent compound is 3-methyl-5-[2-(3-tret.butylamino-2-hydroxypropoxy) phenoxymethyl]-1,2,4-oxadiazole (Compound 1, prodolol) which is superior to propranolol, oxprenolol, and particularly labetalol in its beta-adrenoceptor blocking activity.

[The new antidepressant tetrindole].

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.

[The effect of antihistaminic preparations on the binding of labelled mepyramine, ketanserin and quinuclidinyl benzilate in the rat brain].

The effects of some antiallergic drugs on H1-histamine, 5-HT2-serotonin, and M-cholinoreceptors ligand binding in the rat brain were studied in vitro. Dimedrol, dimebon, and phencarol bonded to H1-receptors: IC50 were 76 +/- 10, 153 +/- 15, 320 +/- 60 nM, respectively. Diazoline and dimebon had some affinity for 5-HT2-receptors, its IC50 was 880 +/- 90 nM.

[Anticalcium activity of several antidepressive agents].

In experiments in white mice and rats the antidepressants pyrazidol (pirlindole), moclobemide and especially tetrindole possess anticalcium activity in tests of calcium chloride-induced lethality in mice and arrhythmia in rats. Tetrindole is as active as verapamil. Imipramine, azaphen and incazane were not active in these experiments.

[The antiamnesic properties of antidepressants].

The experiments on albino rats demonstrated that antidepressants pyrazidol, imipramine, incazane, moclobemide and to a lesser degree azaphen reduce the amnesic effects of electroshock and scopolamine in the rats with the acquired conditioned reaction of passive avoidance. The studied antidepressants decrease also the disturbing action of alcohol on the learning of rats of the conditioned reaction of active avoidance.

[Effects of antidepressive agents on tolerance of hypoxia and physical exercise].

In experiments on mice and rats we studied the influence of antidepressants on hypoxic and physical tolerance. The antidepressants pyrazidol, azaphen, imipramine and moclobemide as well as the nootropic drug piracetam prolonged the life of animals in conditions of hypoxic and hemic hypoxia and increased the survival rate of rats in circulatory hypoxia. In experiments on mice antidepressants increased also the time of swimming.

[The comparative influence of pyrazidol, inkazan and other antidepressant monoamine oxidase inhibitors on the pressor effect of tyramine].

In experiments on conscious normotensive male Wistar rats the new antidepressants, reversible MAO-A inhibitors, pyrazidole and incazane, as well as moclobemid increased the pressor effect of orally administered tyramine. The drugs potentiated also the pressor effect of intravenous tyramine. More prolonged potentiation of tyramine action was produced by moclobemid, less prolonged by incazane.

Active immunization against bioregulators: behavioural and catecholamine changes in albino rats immunized against sydnophen.

Active immunization of white rats against the catecholamine analogue, sydnophen, results in physiological changes extending over two months. The levels of noradrenaline in blood, and dopamine in brain, were depressed, some behavioural activities were reduced and alcohol consumption was lowered. On this basis, active immunization against various bioregulators--a method of inverse regulation--shows promise as a method for achieving long-term adjustment of physiological status.

[The immunization of white rats with a covalent conjugate of sidnofen and serum albumin suppresses chronic ethanol consumption].

The influence of white rats of alcohol abuse formation of immunization by covalent conjugates of serum albumin with psychostimulant sydnophen was investigated. Immunization by conjugates where the molar sydnophen: protein ratio was 18:1-33: 1 results in significant depression of 15% ethanol consumption (in the condition of free choice between water and ethanol solution).

[The effect of pyrazidol and inkazan on the rotation behavior of rats].

Effect of some MAO inhibitors on rotational behavior induced by d-amphetamine in unilaterally 6-OHDA-lesioned rats was studied. Among all MAO inhibitors tested only 1-deprenyl induced rotational behavior. Nialamide, chlorgiline, pyrazidol and inkazan dose-dependently enhanced rotational behavior induced by 2 mg/kg i.

[Immunocorrection of the physiologic status of white rats by sidnofen conjugates with bovine serum albumin].

The effect of immunisation by covalent conjugates of known psychostimulant and antidepressant sydnophen with bovine serum albumin (BSA) on behaviour, formation of conditioned reflex reactions and alcoholization of white rats has been studied. The immunization of sydnophen with BSA by conjugates permits to obtain a long-term alteration of the emotional status: suppression of behavioral activity, learning and alcohol attraction of rats similar in some elements to the action of neuroleptic drugs. The direction of these alterations is opposite to ones caused by the action of sydnophen.

[Effect of piracetam on the action of antidepressants (experimental data)].

Experiments were performed on mice. Piracetam (500 mg/kg orally), but not meclofenoxate (100 mg/kg orally) potentiated the activating effect of antidepressants: pyrazidol, inkazane, nialamid and imipramine (10 mg/kg orally), in the "behavioral escape" test.