[Intermuscular myxoma of the pelvis].
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Biomedical subjects
Publications and source records attributed to N I Andreeva.
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The novel antidepressant tetrindole (2,3,3a,4,5,6-hexahydro-8-cyclohexyl-1H[3,2,1-j,k] carbazole) was found to be a selective inhibitor of monoamine oxidase A (MAO A). In vitro it inhibited rat brain mitochondrial MAO A in a competitive manner with Ki value of 0.4 microM. A 60 min preincubation did not change the competitive mode of interaction between enzyme and tetrindole (Ki value was 0.27 microM). The inhibition of rat brain mitochondrial MAO B was of mixed type with Ki value of 110 microM. Dilution or dialysis of mitochondrial suspension did not restore MAO A activity after inhibition by tetrindole both in vitro and in vivo, whereas inhibition of MAO B in vitro was completely reversible. Oral administration of tetrindole inhibited rat brain and liver mitochondrial MAO A by 80% within 0.5-1 hr and the onset of recovery of enzyme activity became evident after 24 hr. A small inhibition of MAO B (-20-30%) was observed in isolated brain and liver mitochondria within 1-6 hr and enzyme activity had completely recovered after 16 hr. The data obtained indicate that antidepressant activity of tetrindole may be explained by selective inhibition of MAO A, however an apparent discrepancy between competitive manner of MAO A inhibition in vitro and poor recovery of enzyme activity in vivo does not allow us to decide whether tetrindole is a "tight-binding" reversible inhibitor or a selective irreversible inhibitor of MAO A.
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. In vitro on isolated intestinal segments of guinea-pigs tetrindole exerts anticalcium action, but in less degree than verapamil. In all probability the anticalcium activity of tetrindole may play some role in the mechanism of action of this compound on the central nervous system.
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.
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.
Antidepressants pyrazidol (pirlindole), incazan, imipramine, nialamide, nomifensine, mianserin were shown to reduce the duration of immobilization in mice in "despair" tests and increase the number of rotations in water "escape" tests.
Combined use of carbamazepine (unlike valproat-Na) and antidepressants pyrazidole (pirlindol) or imipramine increased anticonvulsive and antireserpine activity.
Orally administered amitryptiline (25 and 50 mg/kg) protected animals against fatal convulsions induced by thiosemicarbazide, strychnine and metrazole. Vilaxazine had a protecting effect against death induced by strychnine. Impramine, maprotiline, mianserine and pirlindole (pyrazidol) only somewhat prolonged the latend period of convulsions and death, while incazane, caroxazone, nomifenzine and trazodone had practically no effect on the action of the three convulsants under study.
A considerable blastomogenic effect of metabolite serotonin 5-methoxytryptamine (5-MOT) subcutaneously administered for a long time to C57BL/6 mice was established. This effect was decreased noticeably if the further metabolism of 5-MOT into 5-methoxyindolyl-3-acetic acid (5-MIAA) was blocked by pyrazidol. These results explain the fact that the blastomogenic effect of 5-MOT is not direct but is caused by the transformation of 5-MOT into its final carcinogenic metabolite 5-MIAA.
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.
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