Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR and CoMFA analysis.

A series of pyrazinocarbazoles, analogues of short acting antidepressant pirlindole (2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride), were tested as inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B). Rigid analogues exhibited potent and selective inhibition of MAO-A and have size limits (X:Y:Z) of 13.0 x 7.

N-alkyloxycarbonyl derivatives of ethylene diamine as monoamine oxidase inhibitors.

A series of urethane type derivatives of ethylene diamine (EDA) was synthesised and tested as inhibitors of monoamine oxidase (MAO) A and B. Nature of aromatic ring and a position of substituents in it were important for the inhibitory activity. Chlorobenzyloxycarbonyl-EDA derivatives exhibited selective inhibition of MAO-A with 3,4-Cl2-C6H4CH2OCO-EDA being a most potent and selective MAO-A inhibitor (IC50 4 microM).

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.

[DNA-methylase activity in human cardiac muscle. Association of DNA methylase activity with actin protein fractions].

The column isoelectrofocusing activity of the nuclear extracts of the human cardiac muscle has revealed at pH 3.5-8.2 5 peaks of DNA-methylase.

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.

[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.

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.

Lipid peroxidation affects catalytic properties of rat liver mitochondrial monoamine oxidases and their sensitivity to proteolysis.

1. Lipid peroxidation (LPO) in rat liver mitochondria decreased the activity of monoamine oxidase (MAO) with physiological substrates serotonin and 2-phenylethylamine (by 15-30%) and induced deamination of glucosamine, which was highly sensitive to selective MAO A inhibitor pirlindole. 2.

[Multiple forms of monoamine oxidase in the growing human placenta].

A ratio between two types of monoamine oxidase (MAO) was studied in the mitochondrial fraction of growing human placenta: MAO-A which is predominant in the tissue and the minor MAO-B. Activity of MAO-A with serotonin as a substrate was statistically distinctly lower (by 22%) in placenta within early periods of pregnancy as compared which the mature placenta during the delivery time. In the growing placenta activity of MAO-B with benzylamine as a substrate reached 365% of the MAO-B activity in the mature placenta.

[Natural modulators of the function of the amine oxidase system in the body].

In cerebrospinal fluid (CSF) obtained from patients with chronic alcoholism natural modulators of monoamine oxidase (MAO) activity, containing in human mitochondrial and microsomal fractions or in rat brain mitochondria, have been found. These modulators, which were previously unknown, did not affect the activity of partially purified diamine oxidase from human placenta with 14C-putrescine as a substrate. The MAO modulators from CSF were thermostable (during 3 min at 100 degrees), penetrated through dialysing membrane thus differing from high molecular modulators of MAO previously described.

[Comparative characteristics of membrane bound and cytoplasmic monoamine oxidases in human placenta].

Catalytic and physico-chemical properties of human placental monoamine oxidases (MAO) were studied. Both forms of the enzyme, membrane-bound and soluble, exhibited similar properties: optimal activity at pH8.3, equal rate of inhibition with selective MAO inhibitors, identical substrate specificity (the best substrate--serotonin).

[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.

[Interaction of placental diamine oxidase with carboxyl-substituted lysine].

The interaction between diamine oxidase (DAO) of human placenta and carboxyl-substituted lysines, including N-terminal lysine containing peptides, occurs at rather a high rate and is characterized by the following features. First, the enzyme catalyzes the oxidative deamination of one amino group in the N-terminal lysine at a rate which is inversely proportional to the peptide length. Second, the bound derivatives induce a noncompetitive reversible inhibition of DAO which is enhanced during their coincubation.

[Amine oxidases of the human placenta].

Some current advances in studies of human placenta amine oxidases monoamine oxidase (MAO), diamine oxidase (DAO) and benzyl amine oxidase are reviewed. Localization of these enzymes in placental tissue as well as distribution in subcellular fractions (mitochondria, microsomes and cytosol) are considered. Presence of multiple forms of MAO in placenta is discussed: three types of MAO A, B and B' were found in human placenta, while MAO of the B' type was not detected in other mammalian tissues.

[Unusual inhibition of monoamine oxidase activity induced by clorgyline].

The phenomenology of inhibition of FAD-containing type A monoamine oxidase by clorgyline solutions containing negligibly small amounts of clorgyline that are insufficient for stoichiometric covalent blocking of a perceptible amount of the coenzyme was studied. The nature of this phenomenon consists in the fact that at monoamine oxidase concentrations of about 10(-8) M, more than 50% of the enzyme activity in inhibited by clorgyline (less than or equal to 10(-10) M), although is accordance with a well-defined mechanism after monoamine oxidase-catalyzed tautomerization clorgyline presumably interacts with FAD at a 1:1 stoichiometric ratio. This effect termed as secondary inhibition seems to be induced not by clorgyline proper, not by changes in the solvent induced by this compound.

[Oxidation of p-nitrobenzylamine and p-dimethylaminomethylbenzylamine by amine oxidases from the human placenta and serum].

Oxidation of p-nitro- and p-dimethylaminomethyl derivatives of benzylamine, catalyzed by amine oxidases from human placenta and blood serum, was studied. The amine oxidase activity was estimated by means of a spectrophotometric procedure involving measurement of aldehyde formed during the reaction after extraction with hexane. For extraction of benzaldehyde and p-nitrobenzaldehyde in the samples HCl was added up to the concentration of 0.

[Modified radiometric method of determining amine oxidase activity].

A modified radiometric procedure is developed for estimation of amine oxidase activity. The method avoids withdrawal of samples in order to measure the radioactivity of reaction products. The enzymatic reaction, extraction of the products and measurement of the radioactivity were carried out in the same scintillation vials.

[Subcellular localization, inhibiting specificity and catalytic properties of several aminooxidases from the human placenta].

Human placenta was shown to contain practically all known types of aminooxidase, i.e., Membrane-bound and soluble monoamine oxidases A that predominantly oxidize serotonin (Km approximately 0.

[Decrease of placental amine oxidase activities in premature birth].

48 women with normal (38-40 weeks) and premature (38-37 weeks) labor were examined. The rate of deamination of serotonin, tyramine, beta-phenylethylamine, putrescine, cadaverine and histamine in samples containing extracts of the control group placenta averaged 0.86; 0.

[Purification and some physico-chemical properties of myocardial adenylate deaminase].

A procedure for isolation of adenylate deaminase from duck heart muscle has been developed. The method includes extraction of enzyme, chromatography on cellulose phosphate, fractionation by ammonium sulfate, chromatography on Sephadex G-25 and ion-exchange chromatography on DEAE-cellulose. The enzyme was purified approximately 4000-fold with a yield of 25%.

[Allosteric modification of adenylate deaminase activity: appearance of adenosine deaminase activity as an effect of potassium ions].

The activation of purified adenylate deaminase from the duck myocardium by K+ is accompanied by modification of the substrate specificity and by the appearance of the capacity to deaminate adenosine and adenine. Adenosine deaminase activity originates at the concentration of K+ of 0.15 M that possesses the most stimulating effect on adenylate deaminase activity; with the increase of potassium ions concentration adenosine deaminating activity is enhanced as well, with a parallel reduction of Hill's constant.