Biomedical subjects
Publications and source records attributed to M D Mashkovskiĭ.
Ten antidepressants belonging to different chemical classes administered to mice for 5 days have been found to be more similar as regards the pharmacological action as compared to the effects attained with a single drug use.
Pyrazidol (2,3,3a,4,5,6-Hexahydro-8-methyl-1-H-pyrazino (3,2,1-j,k) carbazol hydrochloride) blocked selectively the type A monoamine oxidase (MAO) in mitochondria of different human and animal tissues, irrespective of substrate specificity of the type A MAO in the tissues studied. Thus, in tissues containing both types of MAO (rat, bovine and human brain, rat liver and intestine tissues) pyrazidol inhibited selectively the deamination of serotonin and did not affect the deamination of 2-phenylethylamine--the main substrates in these tissues of the type A and the type B MAO, respectively. In human placenta and rat heart containing only the type A MAO, which catalyzes deamination of 2-phenylethylamine, pyrazidol also inhibited the deamination of serotonin, tyramine and 2-phenylethylamine at comparatively low concentrations and in equal degree. Pyrazidol did not affect significantly the type B MAO in bovune liver and kidney tissues, although the latter enzyme catalyzed deamination of serotonin. The degree of inhibition by pyrazidal of dopamine deamination in various tissues depended on the particular type of MAO mainly involved in oxidation of the amine.
The thiol compounds, unithiol, D-penicillamine and cysteine administered per os, produce an antihypertensive effect in spontaneously hypertensive rats and in animals with experimental renovascular and DOCA-induced hypertension. The drugs reduce the pressor effect of angiotensin I and potentiate and prolong the depressor action of bradykinin in anesthetized normotensive rats. As for the activity unithiol and D-penicillamine are found to be superior to cysteine. This is in a good agreement with the drug inhibitory action in respect to dipeptidyl carboxypeptidase, an enzyme that plays the key role in the control of the activity of the renin-angiotensin and kallikrein-kinin systems of the body.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Study of 16 antidepressants, (imipramine, amitryptyline, doxepin, dibenzepin, maprotilin, mianserin, nomifensin, trazodon, caroxazon, adepren, viloxazin, nialamid, asaphen, pyrazidol, inkasan, ftoracizin) in experiments on white mice have shown that the drugs tested may be arranged in the following way as regards the intensity of the mydriatic effect they produce: ftoracizin, amitryptyline, doxepin, imipramine, dibenzepin. Pyrazidol produces a very weak and short-lived mydriatic effect. Adepren, inkasan, caroxazon, adepren produce no mydriatic action.
Of the two optical isomers of sydnocarb, only 1- (or 1R)-isomer exerts a stimulant effect on the central nervous system. By its stimulant action it differs from both optical isomers of amphetamine. The activity of 1-(IR)-sydnocarb as measured by the locomotor excitation test is similar to that of d(1S)-amphetamine but is significantly less powerful as indicated by stereotypy, hyperthermia, anorexigenic action and antagonism to the depressant effects of reserpine.
It has been shown in experiments on unanesthesized rats with normal arterial blood pressure that the antidepressants azaphen, pyrazidol and inkasan as well as imipramine and amitryptyline reduce the hypotensive effect of clofelin. With the dosage build-up the antidepressants themselves start to exert the hypotensive effect. However, the antagonism to clofelin in relation to the arterial blood pressure is maintained. It is suggested that such an effect is consequent on the impairment of noradrenaline neuronal uptake induced by the antidepressants.
In healthy animals and in those with different experimental tumours, the psychostimulant drug sydnophen activates the immune reactions: increases the number of RFC, the intensity of delayed hypersensitivity, blast transformation of lymphocytes, and the QD coefficient. This activation is attended by a slight inhibition of transplanted tumours. The psychostimulant sydnocarb exerts no immunostimulant action or any effect on the growth of experimental tumours.
In rabbit experiments, the local administration of prostaglandins E2 and F2 alpha provoked an increase in intraocular pressure because of hyperproduction of intraocular liquid and increased permeability of the histoophthalmic barrier. Local administration of dicinon and taurin elicited a protective action and prevented the hypertensive effect of prostaglandins. Dicinon and taurin did not produce any influence on spasmogenic and hemodynamic effects of prostaglandins on isolated preparations of smooth muscle organs. Therefore, the protective effect of the drugs in the prostaglandin-induced hypertension of the eye is not related to the antiprostaglandin properties shown by these drugs.
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. A synergic effect on intraocular pressure was observed when proxodolol was combined with pilocarpine and/or klofelin.
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. As cimetidine and ranitidine, the agent accelerated chronic gastric ulcer healing. Quiditene has been allowed for clinical studies in Russia.
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 agent does not greatly differ from labetalol in its alpha-adrenoblocking activity. Proxodolol has been chosen for preclinical and clinical studies.
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. Proxodolol proved to be effective in treating experimental hypertension and arrhythmias. It exhibits anti-ischemic activity.
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. Dimedrol, phencarol and diazoline were found to be active against M-cholinoceptors, but when given in the maximal concentration (10 microM) it acted nonspecifically. In contrast to the other drugs, bicarphen had no effects on the binding of [3H]-mepyramine, [3H]-ketanserine, and [3H]-quinuclidinyl benzylate in the rat brain.
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.
Ionization constants were measured and distribution between the "fatty" and aqueous phases of the drugs (amphetamine, ephedrin, tyramine, methylphenidate, pipradrol), belonging to two groups of indirect sympathomimetics differing in the mechanism of their action, was studied. The lipophilic nature of the study compounds is shown to correlate with some pharmacological properties determining the difference in action produced by these drugs.
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. In potentiation of 5-HT activity both drugs were approximately equal.