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Results for “MONOAMINE OXIDASE”

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At least 109 records · Page 6Linked to original sources
PubMed1989

Oxidation of analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidases A and B and the inhibition of monoamine oxidases by the oxidation products.

Twenty analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were tested for their capacity to be oxidized by pure monoamine oxidase-A (MAO-A) prepared from human placenta and pure monoamine oxidase-B (MAO-B) prepared from beef liver. Several of the MPTP analogs were very good substrates for MAO-A, for MAO-B, or for both and had low Km values and high turnover numbers. These values were similar to or even better than those of kynuramine and benzylamine, good substrates for MAO-A and MAO-B, respectively. MPTP had relatively low Km values for oxidation by both MAO-A and MAO-B. In contrast, the turnover number for MPTP oxidation by MAO-B was considerably higher than the value for MAO-A. The corresponding pyridinium species of MPTP and several of the MPTP analogs inhibited MAO-A competitively with Ki values at micromolar concentrations; in contrast the pyridinium species inhibited MAO-B competitively at considerably higher concentrations (i.e., 100 microM or greater Ki values). The data provide information concerning the structural requirements for the oxidation of tetrahydropyridines by MAO-A and MAO-B and the inhibition of these enzymes by pyridiniums.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1982

Effects of monoamine oxidase inhibition on female sexual behavior, serotonin levels and type A and B monoamine oxidase activity.

Administration of various monoamine oxidase (MAO) inhibitors to ovariectomized-adrenalectomized, estrogen and progesterone-treated female rats was utilized to study possible relationships between the lordosis response and levels of preoptic-hypothalamic MAO and serotonin (5HT). Depending on the drug and dose, behavioral changes ranged from no effect to complete abolition of the lordosis response. Surprisingly, only those treatments which substantially inhibited both the A and B forms of MAO affected lordosis. However, behavioral deficits were related to increases in 5HT levels in a graded manner. In fact, a sigmoid-shaped dose-response curve was generated by plotting either the lordosis quotient or quality score versus the percent increase in preoptic-hypothalamic 5HT. Proceptivity was reduced by some treatments but not abolished, suggesting that different neurotransmitters may mediate receptive and proceptive components of female sexual behavior. In general, these results support the hypothesis that 5HT may exert inhibitory control over hormone dependent female sexual behavior and suggest that previously reported changes in MAO activity and 5HT levels following gonadal steroid treatment could pay a role in hormonal facilitation of female sexual behavior.

Animals↗
PubMed2002

Differential subcellular location of mitochondria in rat serotonergic neurons depends on the presence and the absence of monoamine oxidase type B.

Monoamine oxidase type A and type B are major neurotransmitter-degrading enzymes in the CNS. The type A is present on mitochondrial outer membranes in the whole extent of noradrenergic and dopaminergic neurons, including their axon terminals. The type B is present in serotonergic neurons, but its subcellular localization has not been elucidated. In the present study, we used both a double-labeling immunofluorescence method and electron microscopic immunohistochemistry to examine the subcellular localization of monoamine oxidase type B in serotonergic neurons projecting from the dorsal raphe nucleus to the suprachiasmatic nucleus in the rat brain. In the dorsal raphe nucleus, serotonin-positive neuronal cell bodies were clustered, and virtually all of these cell bodies were also positive for monoamine oxidase type B. By contrast, serotonin-negative neuronal cell bodies were mostly free of this enzyme. Within the neuronal cell bodies and dendrites that were positive for monoamine oxidase type B, most mitochondria contained this enzyme on their outer membranes, but a substantial proportion of mitochondria lacked this enzyme. In the suprachiasmatic nucleus, serotonin-positive varicosities were concentrated, but none of these varicosities exhibited monoamine oxidase type B. In this nucleus, mitochondria were found in almost all serotonin-positive axon terminals, but monoamine oxidase type B was not observed in any axon terminal that contained mitochondria. Our results show that there are two kinds of mitochondria in serotonergic neuronal cell bodies and dendrites: one containing monoamine oxidase type B on their outer membranes, and the other lacking this enzyme. In addition, mitochondria in serotonergic axon terminals do not possess monoamine oxidase type B. It is suggested in serotonergic neurons that only mitochondria lacking monoamine oxidase type B are transported by axonal flow up to axon terminals. It is also probable that mitochondria containing monoamine oxidase type B are transported along the axons, but that this enzyme undergoes a change, for example, conformational change, decomposition or removal from the membranes.

Animals↗
PubMed1995

Imidazoline/guanidinium binding domains on monoamine oxidases. Relationship to subtypes of imidazoline-binding proteins and tissue-specific interaction of imidazoline ligands with monoamine oxidase B.

Pharmacologically active compounds with an imidazoline and/or guanidinium moiety are recognized with high affinity by a family of membrane-bound proteins collectively known as imidazoline binding sites or imidazoline/guanidinium receptive sites. Two such receptive sites may correspond to imidazoline binding domains identified on the A and B isoforms of monoamine oxidase (MAO), but the detection of monoamine oxidase isoforms in multiple tissues contrasts with the restricted expression of imidazoline-binding proteins. To address these issues, we determined the relationship between monoamine oxidase isoforms and subtypes of imidazoline-binding proteins in human tissues known to express one or both isoforms of MAO. 2-(3-Azido-4-[125I]iodophenoxy)methylimidazoline ([125I]A-ZIPI), a photoaffinity adduct that selectively labels imidazoline-binding proteins, photolabeled an M(r) = approximately 59,000 peptide in liver and an M(r) = approximately 63,000 peptide in placenta, consistent with the M(r) of the MAO isoforms identified by immunoblots in these tissues. The photolabeled species in liver was immunoprecipitated with MAO-B selective antibodies, whereas the photolabeled species in placenta was immunoprecipitated by MAO-A selective antibodies consistent with the isoform of MAO predominantly expressed in these tissues. The imidazoline/guanidinium ligands interact with the enzyme at a site distinct from the substrate recognition domain, and the immunoprecipitated peptides in liver and placenta display distinct ligand recognition properties consistent with those reported for subtypes of imidazoline binding sites. However, the imidazoline binding domain was not detected in platelet membrane preparations containing amounts of MAO-B equivalent to those in the photolabeled liver membranes indicating that recognition of this domain is tissue-restricted. Restricted access to the imidazoline binding domain on platelet MAO-B was not altered by membrane washing with 500 mM KCl or by solubilization and partial purification of the enzyme suggesting that there are distinct subpopulations of MAO. Identification of a binding domain on MAO that recognizes this class of pharmacologically active compounds suggests a novel mechanism for regulation of substrate oxidation/selectivity or that the enzyme may subserve an as yet undefined function.

Affinity Labels↗
PubMed1986

Inhibition of monoamine oxidase A-form and semicarbazide-sensitive amine oxidase by selective and reversible monoamine oxidase-A inhibitors, amiflamine and FLA 788(+).

In vitro studies demonstrated that two selective monoamine oxidase (MAO)-A inhibitors, amiflamine and FLA 788(+), have been shown to inhibit semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung homogenates in a concentration-dependent way. The inhibition was not greatly influenced by pretreatment of the preparations with either clorgyline (10(-3) mol/l), l-deprenyl (10(-3) mol/l) or SKF 525A (10(-4) mol/l). The two compounds showed a time-dependent inhibition of SSAO, and for the initial phase of the inhibition, amiflamine is a competitive inhibitor with a Kislope of 135 mumol/l, but FLA 788(+) is a noncompetitive inhibitor with a Ki value of 180 mumol/l. After preincubation for 60 min at 37 degrees C, however, inhibition by amiflamine was found to be essentially irreversible whereas that produced by FLA 788(+) was still noncompetitive and reversible. These two compounds also reversibly and competitively inhibited rat testis MAO-A with FLA 788(+) being much more selective towards this MAO (Kislope = 0.26 mumol/l for FLA 788(+) and 7 mumol/l for amiflamine, respectively). The present results indicate that both MAO-A-selective inhibitors also inhibit SSAO in vitro, but their properties as SSAO inhibitors differ from those as MAO-A inhibitors.

Animals↗
PubMed2005

Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion.

Several multifunctional iron chelators have been synthesized from hydroxyquinoline pharmacophore of the iron chelator, VK-28, possessing the monoamine oxidase (MAO) and neuroprotective N-propargylamine moiety. They have iron chelating potency similar to desferal. M30 is a potent irreversible rat brain mitochondrial MAO-A and -B inhibitor in vitro (IC50, MAO-A, 0.037 +/- 0.02; MAO-B, 0.057 +/- 0.01). Acute (1-5 mg/kg) and chronic [5-10 mg/kg intraperitoneally (i.p.) or orally (p.o.) once daily for 14 days]in vivo studies have shown M30 to be a potent brain selective (striatum, hippocampus and cerebellum) MAO-A and -B inhibitor. It has little effects on the enzyme activities of the liver and small intestine. Its N-desmethylated derivative, M30A is significantly less active. Acute and chronic treatment with M30 results in increased levels of dopamine (DA), serotonin(5-HT), noradrenaline (NA) and decreases in DOPAC (dihydroxyphenylacetic acid), HVA (homovanillic acid) and 5-HIAA (5-hydroxyindole acetic acid) as determined in striatum and hypothalamus. In the mouse MPTP (N-methy-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD) it attenuates the DA depleting action of the neurotoxin and increases striatal levels of DA, 5-HT and NA, while decreasing their metabolites. As DA is equally well metabolized by MAO-A and -B, it is expected that M30 would have a greater DA neurotransmission potentiation in PD than selective MAO-B inhibitors, for which it is being developed, as MAO-B inhibitors do not alter brain dopamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Cannabis extract, but not delta 1-tetrahydrocannabinol, inhibits human brain and liver monoamine oxidase.

Mitochondrial monoamine oxidase (MAO) of human brain and liver was inhibited by low concentrations of cannabis extract (CE) and a cannabinoid fraction isolated from it. delta 1-Tetrahydrocannabinol (THC) did not elicit any inhibitory effect on the enzyme. The inhibition of MAO activity by CE and by its active fraction was more pronounced when the monoamine substrates 2-phenylethylamine (PEA) and benzylamine (BA) were used, as compared to the inhibition of the enzyme activity when 5-hydroxytryptamine was the substrate. The active cannabinoid fraction was found to be more potent than CE in inhibiting the activity of MAO with either substrate. The isolated fraction contains at least two cannabinoids with Rf values of 0.67 and 0.71 on silica gel thin layer chromatography (TLC), as determined with toluene/chloroform/methanol (100:10:1, by volume) as the solvent system. The findings of this study emphasize the need for further exploration of the potential of cannabis as a source for therapeutic agents.

Brain↗
PubMed1992

Abuse of monoamine oxidase inhibitors.

Monoamine oxidase inhibitors, like other antidepressants, generally are considered free of risk for abuse. There is, however, some evidence that MAOIs possess dependence and abuse potential for some patients. We will review the available literature and describe three current cases. Recommendations for treatment are discussed briefly.

Adult↗