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Biomedical subjects

V Z Gorkin

Publications and source records attributed to V Z Gorkin.

At least 19 recordsLinked to original sources
PubMed1995

Interaction of indole derivatives with monoamine oxidase A and B. Studies on the structure-inhibitory activity relationship.

Indole and isatin (2,3-dioxindole) analogues were studied as inhibitors of MAO-A and B. They exhibited reversible and competitive MAO inhibition. Three dimensional structures of the compounds tested were constructed and minimized using PC-based molecular graphic software. The QSAR analysis revealed the requirement of co-planar structure of substituents at C2 and C3 of indole ring for selective MAO-A inhibition, whilst type of bond was less essential. The presence of hydroxy group at C5 of isatin increased selectivity of MAO-A inhibition, however simultaneous insertion of substituents into both positions of indole ring (5-hydroxy-2-phenylindole) led to a decrease of MAO-A inhibition. The planar molecules demonstrating potent MAO-A inhibition have the average sizes 7 A in length and 6 A in width. The MAO B inhibition also depended on the sizes of planar molecules however distribution of electron density in the molecules was another precondition for the selective inhibition of the enzyme.

Animals↗
PubMed1995

[Medico-biological aspects of biochemistry of amines and other nitrogen bases].

The art-of-the-state and possible perspectives for studies of the properties of amine oxidases which are medically significant are briefly outlined. Due to the studies conducted at the Research Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences, the authors discuss the results of studies of the following three problems: 1) modified catalytic properties of amine oxidases in experimental intoxications and abnormalities; 2) natural modulators of amine oxidases; 3) synthetic modulators of amine oxidases.

Amine Oxidase (Copper-Containing)↗
PubMed1995

Influence of ethanol administration on the activity and compartmentation of rat liver monoamine oxidases.

Single-dose ethanol administration to rats caused inhibition of liver mitochondrial monoamine oxidases (MAO) A and B, and an increase in susceptibility of MAO A (but not MAO B) to limited proteolysis. Chronic ethanol feeding resulted in a less distinct alteration in catalytic activity and susceptibility to proteolysis of mitochondrial MAO, but increased the amount of soluble MAO. The sensitivity of membrane-bound MAO to inhibitors (imipramine and chlorpromazine), action of which depends on their lipophilicity and/or hydrophobicity, remained unchanged, compared with controls. Increased amounts of soluble MAO seen after chronic ethanol feeding probably reflect an impairment of insertion of newly synthesized enzyme molecules into the outer mitochondrial membrane, rather than solubilization of MAO from it.

Animals↗
PubMed1994

Monoamine oxidase inhibition by novel antidepressant tetrindole.

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.

Animals↗
PubMed1994

Endogenous stimulation of lipid peroxidation in brain increases proteolytic inactivation of mitochondrial monoamine oxidases.

Stimulation of lipid peroxidation in vivo (in experimental epilepsy and closed cranio-cerebral injury, as models for endogenous stimulation of lipid peroxidation) affects catalytic activity, substrate specificity of mitochondrial monoamine oxidases and increases their susceptibility to trypsinolysis. It is suggested that increased susceptibility to trypsinolysis reflects an appearance of new hydrophilic site(s) in monoamine oxidase molecules which may be responsible for an involvement of the modified enzymes in the deamination of other important nitrogenous compounds (such as gamma-aminobutyric acid) with subsequent impairment of a ratio between inhibition and excitation processes in the brain.

Animals↗
PubMed1992

Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: evidence for a monoamine oxidase A inhibiting component of tribulin.

Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin.

Animals↗
PubMed1991

Studies on mitochondrial metabolic processes in offspring of alcoholized rats--I. Evidence for altered activity and sensitivity to monoamine oxidase-dependent control by biogenic amines of some membrane-bound enzymes.

In the liver mitochondrial fraction of the first generation offspring of alcoholized male rats, decreased activities of monoamine oxidase (MAO) types A and B, rotenone-insensitive NADH-cytochrome c-reductase and succinate dehydrogenase were observed. The MAO-dependent inhibition of rotenone-insensitive NADH-cytochrome c-reductase and succinate dehydrogenase by biogenic amines, incubated with the mitochondrial fraction, was altered in the offspring of alcoholized animals as compared with control rats. The sensitivity of these enzymatic activities towards the inhibitory effect of 5-methoxyindol-3-ylacetaldehyde was markedly increased in the offspring of alcoholized male rats. The data obtained suggest the existence of a genetically determined predisposition of the mitochondrial metabolic processes in the offspring of the alcoholized rats to the effects of ethanol and to the toxic effects of acetaldehyde, formed during ethanol metabolism.

Alcoholism↗
PubMed1991

[The action of befol and its derivatives on monoamine oxidase of different origins].

The effect on deamination of serotonine, dopamine, tiramine and 2-phenylamine of benzamide derivatives befol, moclobemide and LIS-641 was studied. Befol and moclobemide are inhibitors of serotonine deaminating activity of MAO. The different sensitivity of this activity to the effect of the benzamide derivatives in beef or rat brain and human placenta was noted. The inhibition was more distinct in tissue homogenate than in corresponding mitochondrial fractions.

Animals↗
PubMed1990

Some neurobiological mechanisms of the effect of ethanol on offspring of chronically alcohol treated rats.

Mechanisms of genetically determined alcoholic motivation were studied in chronically alcohol treated rats and their offspring using neurochemical, physiological and genetic techniques. Stimulation of the activity of membrane-bound monoamine oxidases, (e.g., in liver or brain), modification of their catalytic properties, partial solubilisation and increased sensitivity towards the transitory inhibiting effect of ethanol were detected in chronically alcohol treated rats, especially in offspring which did not receive chronic alcohol treatment. An altered content of biogenic amines in brain and disturbances of behaviour accompanied impairments in functions of monoamine oxidases. Administration of ethanol was required to restore to normal the disturbances in the neurochemical and physiological parameters studied. The constant presence of ethanol in tissues becomes essential for returning metabolic impairments to normal and may be considered as a molecular basis for the development of alcoholic motivation in offspring of chronically alcohol treated animals. A distinct increase in the expression of the c-fos gene in the brain cortex was observed in offspring of chronically alcohol treated rats after administration of ethanol. The impairments in regulating c-fos gene activity caused by ethanol administration suggest that chronic alcohol treatment of animals may influence the functions of the genome of offspring not subjected to chronic alcohol treatment.

Alcohol Drinking↗
PubMed1987

[Effect of clorgyline on the intensity of lipid peroxidation and on erythrocyte membrane stability in hyperoxia].

Administration of monoamine oxidase type A inhibitor clorgyline to rats before hyperoxia prevented oxygen-induced increase in diene conjugate and Shiff's base brain and plasma levels in hyperoxia. This was due to antioxidative effect of clorgyline which resulted in stabilization of blood cellular membranes. Clorgyline had a normalizing effect on extraerythrocyte hemoglobin level, total peroxidase activity and glucose-6-phosphate dehydrogenase activity in the serum.

Animals↗
PubMed1986

[Formation of the superoxide anion radical during the oxidation of biogenic amines catalyzed by mitochondrial monoamine oxidase].

The studies on the activity of monoamine oxidase from human placenta, using 2-phenylethylamine as a substrate, corroborate the hypothesis on the possible superoxide radical generation upon FAD oxidation at the second (aerobic) stage of monoamine oxidase reaction. It has been shown that hydrogen peroxide, but not other activated O2 forms, was the end product of this reaction. No superoxide radical generation took place in such systems. And therefore, the induction of lipid peroxidation in the presence of catalase was impossible in mitochondrial membranes containing monoamine oxidase and amines oxidized by it.

Biogenic Amines↗
PubMed1985

[Inhibition of brain monoamine oxidase in the rat by multiple pyrazidol administration].

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.

Administration, Oral↗
PubMed1985

[Brain monoamine oxidase in schizophrenia].

The content of SH-groups and substrate specificity have been studied in purified preparations of monoamine oxidase (MAO) from human brain. It has been shown that both in schizophrenic and mentally normal persons MAO occurs in a partially oxidized state. The enzyme contains 2 SH-groups per 10(5) daltons of protein and deaminates MAO substrates (serotonin, beta-phenylethylamine) along with histamine, diamine oxidase substrate. Reduction of the partially oxidized SH-groups of MAO in schizophrenics up to 15 SH-groups per 10(5) daltons of protein (the normal value for human brain MAO) does not eliminate the histamine deaminase activity as is the case in experiments with MAO from the normal brain but, on the contrary, considerably potentiates it. The data suggest certain structural alteration of MAO in schizophrenia.

Brain↗
PubMed1984

[Disorders of the deamination of nitrogenous compounds in the heart muscle in experimental atherosclerosis].

The development of alimentary hypercholesterolemia in rabbits (confirmed by morphometric, electrophysiological and biochemical data) was accompanied by a decrease of the serotonin, benzylamine and tyramine deamination rates in heart muscle mitochondria. At the same time a qualitatively new reaction of cadaverine deamination could be seen in the mitochondria. The data obtained suggest that impairment of deamination of the nitrogenous compounds in atherosclerosis may be due to reversible qualitative modification (transformation) of mitochondrial monoamine oxidase activity. Some of the drugs which decrease the level of lipids in blood serum of hypercholesterolemic rabbits abolished and prevented the impairment of deamination of nitrogenous compounds.

Animals↗