Biomedical subjects
Publications and source records attributed to M D Mashkovskiĭ.
Combined use of carbamazepine (unlike valproat-Na) and antidepressants pyrazidole (pirlindol) or imipramine increased anticonvulsive and antireserpine activity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Pyrazidol, which is chemically 2,3, 3a, 4, 5, 6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k] carbazole hydrochloride (international name pirlindole) administered repeatedly (21 days) to rats at a dose of 25 mg/kg per os maintained the selectivity of its inhibitory effect toward type A MAO. When administered repeatedly the inhibitory effect of pyrazidol was 1.5-2-fold higher than after a single administration. The effect of pyrazidol on rat brain MAO was reversible whatever the route of administration. The enzymatic activity returned to normal within 24 h after the last administration. The data obtained suggest that the capacity of selective inhibiting the deamination of the neurotransmitters such as serotonin and noradrenaline in human brain is of paramount importance for therapeutic effect of pyrazidol.
Explore the source record for details and available documents.
The effects of propranolol, oxprenolol, pindolol, labetalol, and atenolol on the isoproterenol-stimulated slow calcium current as well as on spontaneous slow calcium and fast sodium currents were studied in frog trabeculae by the double sucrose bridge technique. Administration of beta-adrenoblockers in low doses (10(-7)-10(-6)M) antagonized the stimulatory effect of isoproterenol on the slow calcium current (pindolol greater than oxprenolol greater than or equal to propranolol = labetalol greater than atenolol). When administered in high doses (2 X 10(-6)-10(-4)M) the beta-adrenoblockers reduced the slow calcium current. Meanwhile, some of them (propranolol, oxprenolol, labetalol) suppressed the fast sodium current.
It has been demonstrated in experiments on rats that atenolol in a dose of 10 mg/kg exerts an antiischemic action in transitory coronary occlusion lasting 30 minutes followed by reperfusion for 23h and 30 min. The effect manifested in the diminution of the relative area and mass of myocardial necrosis zone and in the dilatation of the left ventricle. Atenolol also produced an antiischemic action in permanent coronary occlusion for 24 h. However, the effect in the latter case was less marked than in transitory occlusion. When injected for permanent occlusion, atenolol (10 mg/kg i. v.) led to a 1.59-fold decrease in the necrosis area and a 2.1-fold decrease (p less than 0.001) when administered for transitory occlusion. The mass of the myocardial necrosis zone also dropped (by 1.65-fold and 2.3-fold, respectively), whereas the degree of dilatation by 2.1- and 2.3-fold, respectively.
Inkasan (3-methyl-8-methoxy-3H, 1,2,5,6- tetrahydropyrazine /1.2.3-ab/-beta-carboline hydrochloride) has pharmacological properties characteristic of antidepressants. The clinical antidepressant effect of inkasan is combined with stimulating action. The drug is primarily indicated for patients in whom adynamic (anergic) disturbances are predominant in the clinical picture of depression.
Experiments were made to study the influence of a new antihistaminic drug phencarol [(quinuclidyl-3) diphenylcarbinol hydrochloride] on gastric secretion in rats. Unlike the blockers of H1-histamine receptors (diphenhydramine, omeril, pyrilamine, and cyproheptadine), phencarol reduces secretion and the content of free hydrochloric acid in the gastric contents. The antacid activity of the drug is similar to that of the H2-receptor blocker, cimetidine. However, phencarol differs from the latter drug in the mechanism of action. The antacid action of phencarol is likely to be the result of its activation effect on diamine oxidase, which leads to a decrease in the content of active histamine in the tissues and diminution of its supply to H2-histamine receptors that control gastric secretion.
Experiments on anesthetized rats were made to study the effects of atenolol and propranolol on cardiac output and distribution of the drugs in the heart, lungs, brain, kidneys, large and small intestines, stomach, liver and skeletal muscles with the use of radioactive carbonized microspheres techniques. Atenolol and propranolol provoked a decrease in cardiac output and raised the total peripheral resistance without a detectable effect on blood pressure. Administration of atenolol brought about a decrease in the renal blood flow whereas that of propranolol in the myocardial blood flow.
Explore the source record for details and available documents.
The effect of new antihistaminic drugs, phencarol and bicarphen, on immunologic reactivity of experimental animals was studied in comparison with diphenhydramine. Phencarol and bicarphen inhibited the delayed type allergic reactions to a greater degree than diphenydramine. Unlike diphenhydramine, phencarol and bicarphen injected simultaneously with test-antigen markedly decreased the number of rosette-forming lymphocytes in the immunocompetent organs (spleen, thymus, lymph nodes). Phencarol, bicarphen and diphenhydramine produced the same inhibitory effect on the content of antibody-producing cells in the spleen of mice.
Pyrazidol (1,10-trimethylene-3-methyl-1,2,3,4-tetrahydropyrazino(1,2-a)indole hydrochloride) in low concentrations (0.005 mM) completely blocks the deamination of serotonin, partially that of tyramine, and does not virtually affect the deamination of 2-phenylethylamine by the mitochondria of intestinal cells. There is evidence for the presence of types A and B monoamine oxidases in the rat intestine. Pyrazidol appears to be a selective inhibitor of type A monoamine oxidase of the rat intestine.
Effect of a new antidepressant pyrazidol (1,10-trimethylene-8-methyl-1,2,3,4-tetrahydropyrazino /1,2-/ indole) on the liver and brain MAO activity of rats was studied in experiments in vivo and in vitro. Pyrazidol selectively blocks type A MAO (the substrates serotonin and noradrenaline) and does not virtually affect or has a far less action on type B MAO (the substrate 2-phenylethylamine).
In electroencephalographic experiments on cats and rabbits it was shown that antidepressants of different chemical classes exhibited different central anticholinergic activity. The antidepressants tested (there were 17 of them) acted differently on the EEG activation by galanthamine (an anticholinesterase drug). Pronouncingly antagonistic to the activating effect of galanthamine were doxepin, phthoracizin, aminotryptilin, imipramine. Next followed (in the regressing sequence) desipramine, lidiomil, mianserin, trazodon, viloxazin, noveril, nomifensin, adepren, caroxazon, nialamide, asaphin, pyrazidol and inkasan did not influence the synchronizing action of galanthamine. The substantial differences in the anticholinergic activity of the antidepressant show that the action upon the central cholinergic system is not an obligate component of the antidepressant effect.
The effect of xanthine derivatives on platelet aggregation, blood coagulation and the rate of thrombus formation has been studied. Some of the compounds have proved to be effective antiaggregative agents both when added to the platelet enriched plasma and administered to the body.
Explore the source record for details and available documents.
Explore the source record for details and available documents.