Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOAMINE OXIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1986

Ontogenesis of multiple forms of monoamine oxidase in rat brain regions and liver.

The postnatal development of total, type-A and type-B monoamine oxidase (MAO) in the brain stem, forebrain and cerebellum, determined with preferred substrates or selective inhibitors, were found to follow different patterns. In the brain regions, MAO-A activity reached adult levels in the brain stem first, followed by the forebrain and cerebellum, while MAO-B reached adult levels in these regions at about the same time and later in postnatal life. On the other hand, both MAO-A and B activities were almost fully developed in the newborn liver. Moreover, total and type-A, but not type-B, showed a caudal-to-rostral sequence of biochemical maturation in the brain. The spatiotemporal pattern of differentiation of type-A and type-B activities in the brain tends to support the classification of brain MAO into two distinct isoenzymic forms.

Animals↗
PubMed1982

beta-Carbolines as selective monoamine oxidase inhibitors: in vivo implications.

The inhibitory action of a range of beta-carbolines on human and rat monoamine oxidase (MAO) A and B has been studied. Concentrations of 5-hydroxytryptamine and phenylethylamine, approximately at their Km values, were used as substrates for MAO A and B respectively. A wide variation in selectivity was found, with harmaline being 10,000 times more potent an inhibitor of A than B whereas, using tetrahydro-beta-carboline and harmane, the difference was nearer to ten-fold. Of the carbolines which have been found endogenously, tetrahydro-beta-carboline, 6-methoxytetrahydro-beta-carboline and harmane are all sufficiently potent inhibitors of human MAO A, with I50 values of 5 X 10(-6), 10(-6), 5 X 10(-7) M respectively, for this property to be of possible physiological significance. Harmane, with an I50 of 5 X 10(-6) M, might also play a role as an inhibitor of MAO B.

Animals↗
PubMed1998

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). Within the compounds studied, 3,4-dichloro-benzyloxycarbonyl-EDA exhibited most potent inhibition of MAO-A. This compound inhibited the activity of rat liver MAO-A non-competitively with Ki (slope) value of 3.6 microM, whereas the inhibition of rat liver MAO-B was competitive with Ki (slope) value of 56 microM (not shown). 2.4-Dichlorobenzyloxycarbonyl-EDA also inhibited rat liver MAO-A in a non-competitive manner with Ki of 14.6 microM.

Animals↗
PubMedDate not supplied

[The effect of long-term administration of isatin and himantan to mice on sensitivity of brain monoamine oxidase B to inhibition by deprenyl in vivo and in vitro].

Chronic administration of a low dose of reversible monoamine oxidase (MAO) B inhibitors isatin or himantane (20 mg/kg) to mice during 21 day did not influence the enzyme activity assayed in isolated brain mitochondria. However in vivo sensitivity of brain MAO B to irreversible mechanism-based inhibitor deprenyl injected to animals right after the last administration of the reversible inhibitor sharply decreased. This suggests accumulation of these compounds (or their metabolites?) in the brain accompanied by increased protection of active site of MAO B against specific irreversible inhibitor. deprenyl. In vitro inhibition of MAO B activity in mitochondria isolated from brain of mice treated with isatin or himantane was somewhat higher than in control mitochondria. The latter suggests that long-term treatment of animals with reversible easily dissociating inhibitors may influence regulatory properties of MAO B.

Adamantane↗
PubMed1986

Inhibition of monoamine oxidase by 3,4-dihydroxyphenylserine.

The effects of diastereomers of 3,4-dihydroxyphenylserine (DOPS) on the enzyme activity of monoamine oxidase (MAO) in human placenta and liver mitochondria were examined. Both L- and D-threo-DOPS were found to inhibit MAO-A in human placental mitochondria in competition with the substrate, and the Ki values for L- and D-threo-DOPS obtained were 68.3 and 125 microM, respectively. The inhibitory effect of L-threo-DOPS on both MAO-A and -B activity was confirmed in human liver mitochondria, and MAO-A was found to be more sensitive to the inhibitor. Other isomers of DOPS, L- and D-erythro-DOPS, were found to inhibit MAO activity, but the inhibition was noncompetitive with the substrate. The inhibitory effects of DOPS isomers were not affected by the presence of NSD-1055, an inhibitor of aromatic L-amino acid decarboxylase, suggesting that the inhibition is the direct effect of DOPS, and not of norepinephrine produced by the decarboxylase.

Clorgyline↗
PubMed1977

Procaine hydrochloride as a monoamine oxidase inhibitor: implications for Geriatric therapy.

The results of in vitro experiments showed that inhibition by procaine hydrochloride of monoamine oxidase (MAO) from either rat brain or liver was substrate-dependent. Procaine was more effective in inhibiting serotonin oxidation than phenylethylamine oxidation and had an intermediate effect on tryptamine oxidation. MAO activity in tissue homogenates from rats treated with procaine (150 mg/kg intraperitoneally) was inhibited most in liver, less in heart, and only very slightly brain for a duration of up to 8 hours. Procaine injected in that dose did not alter brain norepinephrine levels and elevated only slightly the brain serotonin levels. It did not protect against the degradation of exogenous radioactive tryptamine in brain. These data confirm and extend prior observations on in vitro inhibition of MAO by procaine and suggest that in high doses procaine may inhibit MAO weakly in vivo. If the reported usefulness of procaine preparations in treating geriatric patients indeed depends upon MAO inhibition, more effective inhibitors would seem to be available.

Aged↗
PubMed2005

LED fluorescence spectroscopy for direct determination of monoamine oxidase B inactivation.

In this work, we report an alternative assay for the determination of the inhibitory effect on monoamine oxidase B (MAO-B) activity of probe compounds. Enzyme MAO-B exhibits fluorescence emissions when it is excited at 412 nm. Using an inexpensive blue LED-like excitation source, we measured the quenching of fluorescence intensity of MAO-B enzyme during the reaction with inhibitors. The applicability of the procedure is demonstrated by assays with l-deprenyl and berberine as inhibitors through the use of fluorescence studies. The IC(50) values of l-deprenyl and berberine were 0.04 and 90 microM, respectively. The K(I) values were 0.020 and 47 microM for l-deprenyl and berberine, respectively. These IC(50) and K(I) values were similar to the values obtained with a standard method. These results demonstrate the feasibility of this method as an alternative to follow the inhibitory effect on MAO-B.

Animals↗
PubMed1985

Enzyme-activated irreversible inhibitors of monoamine oxidase: phenylallylamine structure-activity relationships.

Seventeen 2-aryl-3-haloallylamine derivatives were prepared and evaluated as inhibitors of monoamine oxidase (MAO, EC 1.4.3.4). The synthesis of these compounds was achieved from either alpha-methylstyrene or ring-substituted phenylacetic acid derivatives. With one exception, these 2-arylallylamines were found to be enzyme-activated, irreversible inhibitors of MAO. The most potent inhibitors were ring-substituted derivatives of (E)-2-phenyl-3-fluoroallylamine with IC50 values ranging from 10(-6) to 10(-8) M. Selectivity for the A and B form of MAO was found to depend on the nature of aromatic ring substitution. In general, hydroxyl substitution favored the inactivation of the A form of MAO, while very selective B inhibitors were obtained when the aromatic ring was substituted with a 4-methoxy group. (E)-2-(4-Methoxyphenyl)-3-fluoroallylamine and (E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine proved to be in vitro as selective for the B form of MAO as deprenyl.

Allylamine↗
PubMed1983

[Effects of oxygen and drugs on monoamine oxidase in the dog liver].

The substrate specificity and effects of oxygen concentration and inhibitors on dog liver mitochondrial monoamine oxidase were investigated. MAO activity was determined by measuring oxygen uptake by Warburg's manometer. Dog liver mitochondrial MAO oxidized tyramine most strongly, but oxidation of serotonin, benzylamine and beta-phenylethylamine by this enzyme was found to be very weak, showing less than 30% that of tyramine oxidation. Clorgyline and harmine showed slight inhibition of oxidation of all substrates used in this experiment; however, deprenyl and pargyline strongly inhibited the oxidation of tyramine. The affinity of MAO towards oxygen was found to be strongest with benzylamine as substrate and weakest with hexylamine, and it was intermediate with serotonin. The differences in affinities towards oxygen of this enzyme with various substrates were not changed with any MAO inhibitors added to the reaction mixture. These results suggest that MAO in dog liver mitochondria belongs to type B MAO because of the characteristic behavior of this enzyme to inhibitors. It is suggested that the multiplicity of MAO, which is characterized by substrate and inhibitor specificities, is different from the multiplicity, which is characterized by the affinities towards oxygen.

Animals↗
PubMed2004

Comparison of the binding of the irreversible monoamine oxidase tracers, [(11)C]clorgyline and [(11)C]l-deprenyl in brain and peripheral organs in humans.

The monoamine oxidase A and B (MAO A and B) radiotracers [(11)C]clorgyline (CLG) and [(11)C]L-deprenyl (DEP) and their deuterium labeled counterparts (CLG-D and DEP-D) were compared to determine whether their distribution and kinetics in humans are consistent with their physical, chemical and pharmacological properties and the reported ratios of MAO A:MAO B in post-mortem human tissues. Irreversible binding was consistently higher for DEP in brain, heart, kidneys and spleen but not lung where CLG >DEP and not in thyroid where there is no DEP binding. The generally higher DEP binding is consistent with its higher enzyme affinity and larger free fraction in plasma while differences in regional distribution for CLG and DEP in brain, heart, thyroid and lungs are consistent with different relative ratios of MAO A and B in humans.

Adult↗
PubMed1988

Inhibition of type A monoamine oxidase by methylquinolines and structurally related compounds.

A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4-MQ and 6-MQ inhibited type A MAO (MAO-A) competitively and 7- and 8-MQ inhibited MAO-A noncompetitively. Among these four isomers of MQ, 6-MQ was the most potent inhibitor; the Ki value toward MAO-A was 23.4 +/- 1.8 microM, which was smaller than the Km value toward kynuramine, an amine substrate, 46.2 +/- 2.8 microM. On the other hand, MQ were very weak inhibitors of type B MAO (MAO-B) and 8-MQ did not inhibit MAO-B in brain synaptosomal mitochondria. The inhibition of MAO-A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO-A or -B was confirmed further with human liver mitochondria as sources of MAO-A and -B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO-A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined.

Adrenal Gland Neoplasms↗
PubMed1983

Presence of 5-hydroxy-indolacetic acid in Diloboderus abderus larvae without monoamine-oxidase-like activity.

The authors confirmed the presence of monoamines and 5-hydroxy-indolacetic acid (5-HIAA) in the cephalic region of Diloboderus abderus larvae employing a high pressure liquid chromatography (HPLC) with electrochemical detector. An anticholinesterase insecticide produced an increase in the serotonin and 5-HIAA endogenous levels, and did not modify the catecholamines. Monoamine-oxidase activity was undetectable with a radioactive method using 3H-tyramine as substrate.

Animals↗
PubMed1998

Structure-function relationships of mitochondrial monoamine oxidase A and B: chimaeric enzymes and site-directed mutagenesis studies.

To gain insight into the structure of monoamine oxidases (MAO) A and B, we investigated the properties of various chimaeric enzymes, engineered by moving progressively the junction between the NH2- and the COOH-termini of each MAO form. Whereas exchange of the ADP-binding sequence did not modify the catalytic properties of either MAO isoforms, chimaeras with increasing length of the NH2-terminus of MAO-A (up to position 256) showed a marked decrease in affinity towards substrates and inhibitors. Two sequences, spanning position 62 to 103 and 146 to 220, appeared of particular importance in putatively constituting the binding site of MAO-B. Conversely, the catalytic properties and specificity of MAO-A were insensitive to substitution of both the NH2-(up to position 112) and COOH-termini (from residue 395), but further modification of the central sequence of MAO-A was not compatible with activity. None of the engineered chimaeras showed a shift in substrate and inhibitor specificity. Investigation on MAO-B by site-directed mutagenesis revealed that His382 and Thr158 may represent residues relevant for MAO-B catalytic mechanism.

Amino Acid Substitution↗
PubMed1991

Gossypol effects on monoamine oxidase (MAO) activity in several organs of term rats.

In order to study the effect of gossypol on the monoamine oxidase (MAO) activity in pregnant rat organs, 20 day pregnant rats were sacrificed, and MAO activity/0.02 g tissue of several organs and total MAO activity/organ, were determined. The control group (n = 5) were injected with vehicle intramuscularly on the 17th, 18th and 19th day of pregnancy, and the gossypol treated group (n = 4) were injected with gossypol acetic acid (GAA) (25 mg/kg of body weight) intramuscularly on the 17th, 18th and 19th day and were decapitated on the 20th day of pregnancy. Maternal liver, uterus, placenta, and fetal liver were collected and examined. In placenta, total MAO activity/organ was significantly (p less than 0.05) lower in the GAA treated group than that in the control group. However, in maternal liver, uterus and fetal liver, there was no significant difference in total MAO activity/organ between the two groups. There was no significant difference in MAO activity/0.02 g tissue (specific activity), weight of organ, protein weight/organ and protein/g tissue between the two groups in maternal liver, uterus, placenta and fetal liver. These results suggest that, after intramuscular injection of GAA, total MAO activity/organ in the placenta of pregnant rats might decrease significantly.

Animals↗
PubMed1995

Estrogenic control of monoamine oxidase A activity in human neuroblastoma cells expressing physiological concentrations of estrogen receptor.

Several lines of evidence support the hypothesis of a role played by estrogens in the manifestation of affective disorders in women. The analysis of the mechanism of action of a number of antidepressant drugs clearly demonstrated the involvement of the catecholaminergic system in the etiology of these complex behavioral pathologies. The present in vitro study was therefore undertaken to investigate the presence of a functional link between estrogen and catecholamine metabolism in cells of neural origin. The model system utilized was a human neuroblastoma cell line which was obtained by stable transfection of the estrogen receptor cDNA (SK-ER3). The present study shows that in SK-ER3 activation of the estrogen receptor correlates with a marked decrease in monoamine oxidase A activity. This effect is observed following treatment with a physiological concentration of 17 beta-estradiol and can be blocked by the specific antagonist of the steroid receptor, ICI 182,780. Dibutyryl cyclic AMP acting, like estrogens, on the state of differentiation of SK-ER3 cells did not affect monoamine oxidase A activity. The present study provides strong evidence of a strict relationship between estrogen receptor and monoamine oxidase A activity in human cells of neural origin, thus favoring the hypothesis of an antidepressive effect of estrogens exerted via inhibition of the monoamine oxidative pathway.

Brain Neoplasms↗
PubMed1996

Characterization of rat monoamine oxidase A with noncovalently-bound FAD expressed in yeast cells.

The FAD-binding cysteine of rat liver monoamine oxidase A (MAO A), Cys406, was converted to an alanine by site-directed mutagenesis of the cDNA. The wild-type and mutated enzymes were expressed in yeast cells and catalytic activities were assayed, using as substrates serotonin, tyramine, and kynuramine. Specific activities of the Ala-mutant for these substrates, calculated as the activities per pargyline-sensitive molecule, were about half of those of the wild-type enzyme. The Km values of the mutant enzyme for the substrates were similar to those of the wild-type enzyme. An adduct between FAD and pargyline, a mechanism-based inhibitor, was attached to the apoprotein in the wild-type enzyme, while in the Ala-mutant it was detached from the apoprotein, thereby indicating the presence of noncovalently bound FAD in the mutant enzyme. The Ala-mutant rapidly lost activity during incubation, whereas the wild-type enzyme retained the initial activity. Partial protection from inactivation occurred in the presence of FAD, but not of FMN. Recovery of the enzyme activity was nil when FAD was added after the inactivation. Thus, while the covalent attachment of FAD in MAO A is not required for the catalytic activity, it may function as a structural core for the active conformation in the membrane.

Alanine↗
PubMed1998

Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain.

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Preferential inhibition of the B-form of monoamine oxidase in the liver of rats given 3'-methyl-4-dimethylaminoazobenzene in the diet.

A and B-form monoamine oxidase (MAO) activities were measured in the liver of rats maintained with a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). A-form MAO activity was similar to the control value throughout the feeding periods with serotonin as substrate. In contrast, B-form MAO activity decreased rapidly and the level of MAO activity was maintained at about 30% with beta-phenylethylamine (beta-PEA) as substrate. 3'-Me-DAB feeding did not cause any changes in MAO activity in the brain of rats. A single administration of 3'-Me-DAB (100 mg/kg p.o.) failed to alter A and B-form MAO activities for up to 4 days after its administration. The mechanism of inhibition of B-form MAO activity in rat liver mitochondria by 3'-Me-DAB was investigated. The inhibition of 3'-Me-DAB of B-form MAO activity, in vitro, was competitive and reversible. There was no difference in the apparent Michaelis constant toward beta-PEA between control and 3'-Me-DAB fed rats. B-form MAO in rat liver mitochondria was titrated with (-)deprenyl; this compound is selective to and an irreversible inhibitor of B-form MAO. The content of B-form MAO in liver mitochondria of rats fed 3'-Me-DAB for 3 weeks was decreased to about 60% of the control level.

Animals↗