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 163 records · Page 9Linked to original sources
PubMed1985

Inhibition of monoamine oxidase selectively in brain monoamine nerves using the bioprecursor (E)-beta-fluoromethylene-m-tyrosine (MDL 72394), a substrate for aromatic L-amino acid decarboxylase.

(E)-beta-Fluoromethylene-m-tyrosine (FMMT) is a dual-enzyme-activated inhibitor of monoamine oxidase (MAO). The compound is not an inhibitor per se but is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to yield a potent enzyme-activated irreversible inhibitor of MAO, (E)-beta-fluoromethylene-m-tyramine, which shows some selectivity for inhibition of MAO type A. Decarboxylation of FMMT was demonstrated in vitro using hog kidney AADC and in vivo in rats by the ability of alpha-monofluoromethyldopa (MFMD), a potent inhibitor of AADC, to prevent MAO inhibition produced by FMMT. In isolated synaptosomes, FMMT was decarboxylated by AADC, and, furthermore, the compound was actively transported into these isolated nerve endings. An active transport into the CNS has also been demonstrated in vivo by performing competition experiments with leucine. To demonstrate that FMMT is preferentially decarboxylated within monoamine nerves of the CNS, the nigrostriatal 3,4-dihydroxyphenylethylamine (dopamine) pathway of rats was unilaterally lesioned with 6-hydroxydopamine or infused with MFMD. Under these conditions, MAO inhibition produced by orally administered FMMT in the striatum ipsilateral to the lesion or infusion was markedly attenuated. Combination of FMMT with an inhibitor of extracerebral AADC, such as carbidopa, protected peripheral organs against the MAO inhibitory effects and concomitantly enhanced MAO inhibition in the CNS. Such combinations had a greatly reduced propensity to augment the cardiovascular effects of intraduodenally administered tyramine, when compared with FMMT given alone or with clorgyline, a selective inhibitor of MAO type A. The results obtained with FMMT suggest the possibility of achieving selective inhibition of MAO within monoamine nerves of the CNS and, further, suggest that combination of FMMT with an inhibitor of extracerebral AADC will reduce the propensity of this inhibitor to produce adverse interactions with tyramine.

Animals↗
PubMedDate not supplied

[Functional groups of mitochondrial monoamine oxidase].

Functional groups of mitochondrial monoamine oxidase critical for monoamine oxidase activity were investigated by chemical modification of highly purified monoamine oxidase preparations from pig liver by specific inhibitors. The substrate and inhibitory properties of synthesized derivatives of beta-phenylethylamine, containing various acylating and alkylating groups in the p-position of the benzene ring, were studied. It was shown that 4-carbmethoxy-beta-phenylethylamine (I) is readily deaminated by monoamine oxidase, whereas 4-O-acetyl-beta-phenylethylamine (II) is not affected by the enzyme. 4-O-acetyl-beta-phenylethylamine (II) and 4-ethyl-O-chloroacethyl phenol (III) inhibit deamination of tyramine, 4-amino-beta-phenylethylamine, beta-phenylethylamine, 4-chloro-beta-phenylethylamine and serotonin in different degrees. The kinetic studies demonstrated that this inhibition is probably due to the acylating properties of the compounds obtained. Selectivity in inhibition may be accounted for by acylation of the group of monoamine oxidase which is located in the nearest proximity to the nucleophynoamine oxidase which is located in the nearest proximity to the nucleophylic site of monoamine oxidase active centre important for binding of tyramine. This group is neither the imidazole group of histidyl, nor the SH-group of cysteinyl residues of monoamine oxidase protein molecule. Its nature is discussed in the light of the data obtained.

Acylation↗
PubMed2005

Identification of an cysteine-to-arginine substitution caused by a single nucleotide polymorphism in the canine monoamine oxidase B gene.

Monoamine oxidase B catalytically oxidizes biogenic amines such as phenylethylamine and dopamine, and its activity is presumed to be related to particular behavioral traits. In this study, we first identified a single nucleotide polymorphism (T199C) located on the putative third exon of the canine monoamine oxidase B gene, which causes an amino acid substitution from cysteine to arginine. We then examined the allelic frequencies in five dog breeds (Golden Retriever, Labrador Retriever, Maltese, Miniature Schnauzer, and Shiba) and found significant variation among them. The present results suggest that analysis of the monoamine oxidase B polymorphism could be a useful means of elucidating the genetic background of breed-specific behavioral characteristics in dogs.

Animals↗
PubMed1985

Ontogenetic development of the monoamine oxidase activity and of the metabolism of biogenic monoamines in rat brain.

The article examines the ontogenetic development of the monoamine oxidase activity and of the metabolism of the dopamine, noradrenaline and serotonin in the brain of newborn, 10-day-, 20-day- and 2-month-old rats. Monoamine oxidase activity is determined using three substrates: tyramine, serotonin and beta-phenylethylamine. Monoamine oxidase A (substrate serotonin) and the total monoamine oxidase activity (substrate tyramine) are found to manifest identical development, their activity increasing quickly after birth, to reach constant values after the 10th day. The general course of the development during the first ten postnatal days shows that the post partum increase in the total monoamine oxidase activity in rat brain is predominantly due to monoamine oxidase A. Monoamine oxidase B (substrate beta-phenylethylamine) develops after the 10th postnatal day. Evidently monoamine oxidase A plays a decisive role for controlling the level of the biogenic monoamines in the young organism during the first days of the ontogenesis. Investigation of the changes in the content of dopamine, noradrenaline and serotonin in the age groups of the experimental animals chosen reveals a rapid increase in the dopamine and noradrenaline levels even during the first ten days of the ontogenesis. The increased total monoamine oxidase activity and the increased dopamine content correspond to its increased turnover rate during ontogenesis. The turnover rate of noradrenaline remains unchanged between the 10th and 20th postnatal days. The increasing serotonin level between the 20th and 60th post partum days corresponds to its increased turnover rate.

Aging↗
PubMed1986

Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. I. Inhibition by a selective monoamine oxidase-B inhibitor, MD 780236.

In vitro studies of the effect of MD 780236, a selective monoamine oxidase (MAO)-B inhibitor, on a semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung showed that this compound dose-dependently inhibited SSAO activity. The extents of inhibition of MAO-A, -B and SSAO in these two rat tissues by this compound after 30 min of preincubation were found to be MAO-B greater than MAO-A greater than SSAO. This selectivity was also evident in preparations without preincubation. Degree of inhibition of SSAO was not significantly influenced by pretreatment with either 10(-3) M clorgyline, I-deprenyl or 10(-4) M SKF 525A. Inhibition of SSAO was not enhanced by varying the time of preincubation of the enzyme and the compound, indicating direct action on and reversible inhibition of SSAO. The inhibition of SSAO by MD 780236 was non-competitive with or without preincubation, with a K1 value of 110 muM. Although MD 780236 is a selective and "suicide substrate" inhibitor of MAO-B, these present results indicate that this compound may also inhibit SSAO activity, but by a mechanism different from that for MAO-B. These findings confirm an earlier hypothesis that compounds that inhibit both MAO and SSAO have totally different modes of action on these two different amine oxidases.

Animals↗
PubMed1988

The depletion of rat cortical norepinephrine and the inhibition of [3H]norepinephrine uptake by xylamine does not require monoamine oxidase activity.

Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline (10 mg/kg ip) or the pro-drug MDL 72,394 (0.5 mg/kg ip) did not block the amine-depleting action of xylamine (25 mg/kg ip). Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl (10 mg/kg ip), prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974 (1.25 mg/kg ip), a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not protect cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of [3H]norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine (20 mg/kg ip) administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine.

Allyl Compounds↗
PubMedDate not supplied

[Use of selective inhibitors for computer modeling of the monoamine oxidase active site].

Monoamine oxidase (MAO) is an integral protein of the outer mitochondrial membrane, catalysing the reaction of oxidative deamination of monoamines in the central nervous system and peripheral tissues. The present paper reviews data on the structure of MAO, approaches and methods of computer modeling of active site structure, based on the analysis of MAO inhibition by selective inhibitors Flexible molecules, possessing many conformers are useless for computer modeling. Competitive fully reversible MAO inhibitors with rigid structure and limited number of conformers are preferential compounds for these studies.

Binding Sites↗
PubMed1980

A caution in the use of tritiated substrates for monoamine oxidase assays.

A monoamine oxidase assay utilizing generally labeled [3H]serotonin as substrate became nonlinear after only approximately 5% conversion of initial c.p.m. to product. Subsequent analysis showed that a significant proportion of the tritium label was readily exchangeable into water and that monoamine oxidase activity increased release of label as water. The use of generally labeled substrates for oxidase activities is not recommended.

Animals↗
PubMed1987

Quinoline and quninaldine as naturally occurring inhibitors specific for type A monoamine oxidase.

Type A monoamine oxidase (MAO-A) in human placental mitochondria was competitively inhibited by naturally occurring substances, quinoline and quinaldine, using kynuramine as substrate. Quinoline had a higher affinity for MAO than kynuramine. MAO-A in human brain synaptosomal mitochondria was also competitively inhibited by quinoline, while type B MAO (MAO-B) was reversibly and non-competitively inhibited by quinoline. Quinoline inhibited MAO-A much more potently than MAO-B. Of several compounds structurally similar to quinoline, isoquinoline noncompetitively inhibited MAO-A and -B activity.

Binding, Competitive↗
PubMed1985

Treatment of hyperactive children with monoamine oxidase inhibitors. II. Plasma and urinary monoamine findings after treatment.

Urinary monoamines and metabolites as well as plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol were measured in 14 boys (mean age, 9.2 years) with Attention Deficit Disorder With Hyperactivity during an initial placebo period, after four weeks of treatment with either dextroamphetamine sulfate (N=5) or a monoamine oxidase inhibitor (N=9) and at the end of a subsequent two-week placebo "washout" period. Both dextroamphetamine and monoamine oxidase inhibitors produced persistent changes in monoamines and metabolites, which were most marked and consistent for NE and its metabolite 3-methoxy-4-hydroxyphenylglycol. These changes did not correlate in a consistent fashion with clinical response during drug treatment. Moreover, there was rapid clinical relapse following cessation of either treatment while the alterations in NE metabolism remained during the two weeks following drug, further demonstrating the independence of these changes from clinical state. Future studies with dextroamphetamine need drug-free periods that are greater than 14 days to obtain true "baseline" conditions.

Amines↗
PubMed1994

Short review on monoamine oxidase and its inhibitors.

Since monoamine oxidase is an enzyme catalyzing bioactive monoamines, inhibitors of monoamines are expected to prolong the activity of monoamines in tissue. Monoamine oxidase type B is an active form in brain, and its preferential substrate is dopamine that is the most constantly reduced monoamine in Parkinson's disease brain. Therefore, it is natural to expect that monoamine oxidase inhibitors, deprenyl or lazabemide, could exhibit beneficial effects on parkinsonism, i.e. symptomatic effects. This short review summarizes characteristics of monoamine oxidase from biochemical and pharmacological points, and then briefly mentions the situation of clinical evaluation studies of deprenyl and lazabemide in terms of antiparkinsonian effects in Japan.

Antiparkinson Agents↗
PubMed1983

Interaction between cytosolic monoamine oxidase and spin-labeled amphetamine and its modification by clorgyline and pargyline.

Interactions between a monoamine oxidase (monoamine: oxygen oxidoreductase deaminating, EC 1.4.3.4) obtained from rat liver cytosol by high speed centrifugation and a biologically active, spin labeled analog of amphetamine have been analyzed. The acetylenic monoamine oxidase inhibitors, pargyline and clorgyline, have been used to modulate the binding of spin labeled amphetamine. Broadening of electron spin resonance lines induced by immobilization of the probe on binding has been used to determine the concentration of bound probe. Pargyline was found to inhibit binding of spin labeled amphetamine by cytosolic monoamine oxidase. Bound spin labeled amphetamine was also displaceable by pargyline. In contrast, clorgyline enhanced the binding of spin labeled amphetamine to the cytosolic monoamine oxidase preparation. Inhibition or enhancement of amphetamine binding was very rapid and occurred during the reversible stage of interaction between the enzyme and the acetylenic compounds.

Amphetamine↗