Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:001709 (MAO-A)
 2,432 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in heart and aorta which was reversed by dialysis for 18hr. At high concentrations (10(-4)-10(-3)M) benserazide appeared to increase enzyme activity towards and occasionally above control value. These increases became more prominent after long periods of preincubation (especially in the presence of saturating benzylamine concentrations) and remained after dialysis of those homogenates preincubated with benserazide. The administration of benserazide for one or seven days in daily doses of 5-150 mg/kg also inhibited CRAO activity in vivo in a dose-dependent manner, with greater inhibition after seven days treatment. Reversal of inhibition, by dialysis of tissue homogenates from benserazide-treated rats, was much slower than was found with homogenates incubated in vitro with the drug. After benserazide administration to rats, MAO-A activity towards 5-hydroxytryptamine was generally not inhibited, and in fact was significantly increased in some cases. The administration of L-DOPA (250 mg/kg) together with benserazide (40 mg/kg) resulted in a similar degree of CRAO inhibition in aorta and heart to that seen after benserazide alone. These findings are discussed with regard to the use of these drugs in the therapy of Parkinson's Disease, although the paucity of information about the physiological function of CRAO makes the significance of its inhibition by benserazide unclear.
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PMID:In vitro and in vivo inhibition by benserazide of clorgyline-resistant amine oxidases in rat cardiovascular tissues. 709 30

Treatment of bovine brain mitochondrial membranes with iproniazid (Ip) (1 mM, 15 min) inhibited monoamine oxidase (MAO) activity (substrates: 5-hydroxytryptamine, tyramine, dopamine) and significantly (about 7-fold) increased histamine deaminating activity (HDA). A selective inhibitor of MAO-A clorgyline (contrary to deprenyl) prevented the increase in HDA. Ip (200 mg/kg; within 10-16 h after parenteral administration) markedly (about 6-fold) increased the level of the HDA) in brain mitochondria of mice and guinea pigs. At the same time, a decrease in content of histamine (Hi) and increase in content of 5-hydroxytryptamine was noted in the brains of mice. In anesthetized and non-anesthetized guinea pigs Ip decreased (or prevented) the bronchoconstriction and toxic effects caused by Hi. The antihistamine effects of Ip are apparently due to its being able to induce reversible qualitative alteration (transformation) of the catalytic activity of the membrane-bound MAO of type A, which acquires as a result of this transformation potent HDA.
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PMID:Modification of the activity of mitochondrial monoamine oxidases in vitro and in vivo. 734 Apr 62

1. This study was designed to see whether or not increases in monoamine oxidase (MAO) specific activity that follow chronic treatment of rats with L-dihydroxyphenylalanine (L-DOPA) could be modified by benserazide (Ro 4-4602), an inhibitor of L-aromatic amino acid decarboxylase, and to compare the properties of the increased MAO activity with those of control animals. 2. Male wistar rats were treated with L-DOPA (250 mg/kg) and benserazide (40 mg/kg) either alone or in combination for 10 days. 3. The activity of MAO in homogenates of heart, kidney, liver and brain was measured with 5-hydroxytryptamine (5-HT) and benzylamine (BZ). 4. The significant increases in MAO specific activity seen in heart and kidney following L-DOPA treatment could be reduced or prevented by benserazide. 5. Use of the selective MAO inhibitor clorgyline showed that the increases in MAO specific activity, when measured with either 5-HT or BZ were due to an increase in the number of active centres of MAO-A, in the rat heart. 6. There was a significant increase in the Vmax of the enzyme reaction with 5-HT, in the rat heart and kidney homogenates. 7. It is concluded that L-DOPA increases the specific activity of MAO-A in rat heart and kidney as a result of its decarboxylation.
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PMID:The influence of benserazide on changes in monoamine oxidase activity in some rat tissues following treatment with L-DOPA. 734 36

Administration of S-adenosyl-L-methionine (SAM) (200 mg/kg) to adult mice significantly elevated its cerebral levels while the steady-state levels of histamine (HA) and S-adenosyl-L-homocysteine remained unaltered. [3H]HA (1 microCi/10 microliters) was injected intraventricularly (i.vt.) 20 sec, 2, 5, 10 or 20 min prior to sacrifice (1 hr after SAM) and brains were analyzed for [3H]HA, [3H]methylhistamine (MeHA) and [3H]methylimidazoleacetic acid. Brains of SAM-treated mice contained more [3H]HA than vehicle-treated controls at 20 sec, 2, 5 and 10 min (22, 35, 52 and 25%, respectively). [3H]MeHA levels were lower than controls at 20 sec, but higher at 2 and 5 min. Fifteen minutes after i.vt. [3H]histidine, brains of SAM-treated mice contained 47% more [3H]HA and 39% more [3H]MeHA (compared to controls) while [3H]histidine and [3H]methylimidazoleacetic acid levels remained unchanged. SAM treatment had no effect on the activity of cerebral histamine-N-methyltransferase, S-adenosyl-L-homocysteine hydrolase and monoamine oxidase type A (substrate 5-hydroxytryptamine) when tested in vitro, while monoamine oxidase B (substrate phenylethylamine) activity was significantly decreased. In vitro, SAM had no effect on monoamine oxidase A or B. The findings demonstrate that, unexpectedly, the rate of catabolism of HA to MeHA is significantly decelerated in brains containing elevated levels of SAM.
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PMID:Decreased cerebral catabolism of [3H]histamine in vivo after S-adenosylmethionine administration. 745 98

We have examined the changes induced by the monoamine oxidase (MAO; EC 1.4.3.4) inhibitors tranylcypromine, clorgyline, and deprenyl on MAO activity and 5-hydroxytryptamine (serotonin, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in rat brain and blood (plasma and whole blood). The decreases of MAO-A activity observed in the liver and lungs after different doses of clorgyline or tranylcypromine correlated significantly (r > 0.80 in all cases) with the decline of plasma 5-HIAA. This was unaffected by 0.25 and 5 mg kg-1 of deprenyl, indicating that 5-HT was deaminated exclusively in the periphery by MAO-A. It is interesting that very potent and significant correlations (r > 0.75) were found between plasma 5-HIAA and MAO-A activity, 5-HIAA and 5-HT content in brain tissue. These results suggest that plasma 5-HIAA can be used confidently as a peripheral indicator of the inhibition of MAO-A in brain. This may represent a favorable alternative to the analysis of 5-HIAA in CSF in psychiatric patients undergoing antidepressant treatment with nonspecific MAO inhibitors or with the new selective MAO-A inhibitors.
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PMID:Plasma 5-hydroxyindoleacetic acid as an indicator of monoamine oxidase-A inhibition in rat brain and peripheral tissues. 750 85

1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol (TMIQ) was synthesised and tested for activity as a dopamine-depleting agent in rat brain. After intracerebroventricular infusion, TMIQ caused reductions in dopamine concentrations in substantia nigra, striatum, hypothalamus, and dorsal raphe, and reduction in noradrenaline concentrations in locus coeruleus. TMIQ also reduced 5-hydroxytryptamine concentrations in dorsal raphe and substantia nigra, although with a lower potency. Comparisons between TMIQ and MPTP showed that they were approximately equipotent in depleting dopamine in the substantia nigra, hypothalamus, and dorsal raphe. Pretreatment of animals with a combination of monoamine oxidase A and B inhibitors completely prevented the TMIQ-induced reductions in dopamine concentrations in substantia nigra and hypothalamus. Direct unilateral intrastriatal injections of TMIQ produced marked ipsilateral reductions in striatal dopamine, correlating with a behavioural response consisting of turning towards the side of injection. The results suggest that TMIQ should be evaluated further as a possible MPTP-like compound, which may derive from endogenous beta-hydroxylated catecholamines.
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PMID:1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol depletes catecholamines in rat brain. 750 86

We have used intracerebral microdialysis to examine the reversibility of the action of brofaromine, a selective inhibitor of monoamine oxidase-A (MAO, E.C. 1.4.3.4.), on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) output in rat frontal cortex. Brofaromine significantly increased the 5-HT output to about 200% of basal values 4 h after the s.c. administration of 10 and 30 mg/kg (but not 3 mg/kg) and reduced the concentration of 5-HIAA in the dialysate dose-dependently (61%, 53% and 41% of basal value with doses of 3, 10 and 30 mg/kg, respectively). At this time, cortical 5-HT concentration was increased and cortical 5-HIAA concentration was decreased in a dose-dependent manner. Treatment of rats with 10 mg/kg brofaromine plus 2.5 mg/kg of the irreversible MAO-B inhibitor L-deprenyl increased the concentration of 5-HT in the dialysate more than did brofaromine alone (503% vs 206% of the basal value, 4h after administration). Similarly, clorgyline (5 mg/kg) plus L-deprenyl (2.5 mg/kg) increased the concentration of 5-HT in the dialysate to 461% of the control value. This indicates that the concurrent inhibition of both types of MAO increases 5-HT output more than the selective blockade of either enzyme subtype. We have used this characteristic to examine, in vivo, the reversibility of the interaction of brofaromine with MAO-A. The output of 5-HT and 5-HIAA was examined 19-21 h after treatment with L-deprenyl plus clorgyline or L-deprenyl plus brofaromine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo evidence for the reversible action of the monoamine oxidase inhibitor brofaromine on 5-hydroxytryptamine release in rat brain. 754 77

This study examined the influence of selected monoamine oxidase (MAO) inhibitors on basal ganglia neurotransmitters (dopamine and 5-hydroxytryptamine) and neuropeptide (dynorphin) systems of Sprague-Dawley rats. The striatum or substantia nigra or both were used for biochemical determinations. The striatal concentrations of DA, 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC. The levels of striatal and nigral dynorphin A (1-8) (DYN) were determined by radioimmunoassay. The abundance of striatal prodynorphin (PD) mRNA was determined by Northern blot analysis using a cRNA probe. Deprenyl, a MAO-B selective inhibitor (0.25, 0.5, 5, 10 or 20 mg/kg/day, subcutaneously (s.c.) for 4 d) and clorgyline, a MAO-A inhibitor (0.5, 5, 10 or 20 mg/kg/day, s.c. for 4 d) produced a dose-related increase in DA and 5-HT and a decrease in their metabolites in the striatum. Only high doses (20 mg/kg) of deprenyl or clorgyline induced an increase in DYN levels in the striatum and substantia nigra (DYN terminal region); the increased level of DYN was accompanied by an increase in PD-mRNA levels in striatum (DYN cell-body region). Co-administration of low doses (2.5 mg/kg/day, s.c. for 4 d) of deprenyl and clorgyline, that would selectively inhibit MAO-B and MAO-A respectively, produced a marked increase in DA and 5-HT, a decrease in DOPAC and 5-HIAA, an increase in DYN levels in the striatum and substantia nigra and an increase in PD-mRNA levels in the striatum. The results indicate that concurrent inhibition of MAO-B and MAO-A, that results in markedly elevated levels of DA and 5-HT in the striatum, is associated with an increase in dynorphin biosynthesis in the striatonigral neurons.
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PMID:Influence of monoamine oxidase inhibitors on striatonigral dynorphin system: a study with deprenyl and clorgyline. 769 41

The past 2 decades have witnessed an upsurge in the interest in anxiety disorders. Much research effort has been dedicated to panic disorder and obsessive-compulsive disorder. However, it is only very recently that we have begun to understand some of the basic principles about the psychopharmacology of social phobia. Drug classes thus far studied include beta-blockers, nonselective and irreversible monoamine oxidase inhibitors (MAOIs), and benzodiazepines. Beta blockers appear to be of use in specific social phobias, such as public speaking, whereas they are of little use in generalized social phobia. There is considerable evidence suggesting that MAOIs are effective in reducing both social anxiety as well as social avoidance in generalized social phobia. A disadvantage of the conventional irreversible MAOIs is their risk for hypertensive crises when combined with dietary tyramine. Thus far only a small number of studies with selective MAO-A inhibitors, such as moclobemide and brofaromine, have been conducted in social phobia, and the results indicate that both compounds are effective. Drugs exerting selective and specific actions on certain components of, for example, the serotonergic system, can now be studied, and it is hoped that the role of 5-hydroxytryptamine) and other neuronal systems in social phobia can be elucidated. In order to gain more information about selective serotonergic drugs, the first double-blind placebo-controlled study with fluvoxamine was recently published. Preliminary results indicate a reduction in social anxiety after a prolonged treatment period. Finally, the role of peptides in the treatment of social phobia is critically reviewed. The MSH/ACTH analog Org 2766 was investigated in patients suffering from social phobia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recent developments in the psychopharmacology of social phobia. 777 14

A trout liver monoamine oxidase (MAO) cDNA was cloned by screening a cDNA library with a human MAO-A cDNA probe. The trout MAO cDNA encodes 499 amino acids, with a molecular mass of 56.6 kDa. The deduced amino acid sequence of trout MAO shows 70% and 71% identity with those of human MAO-A and MAO-B, respectively. Trout MAO contains the pentapeptide sequence Ser-Gly-Gly-Cys-Tyr, to which the cofactor FAD is covalently bound. Transient expression of the cDNA in COS-7 cells shows that trout MAO oxidizes both serotonin [5-hydroxytryptamine (5-HT)] and beta-phenylethylamine (PEA), unlike human MAO-A and MAO-B, which oxidize only 5-HT and PEA, respectively. The Km for 5-HT is similar for trout MAO (130 +/- 17 mM) and human MAO-A (68 +/- 4 mM). The Km for PEA is similar for trout MAO (12.5 +/- 2.0 mM) and human MAO-B (1.5 +/- 0.2 mM). When 5-HT is used as a substrate, trout MAO is more sensitive to clorgyline (IC50, 2.8 +/- 0.2 x 10(-8) M) than deprenyl (IC50, 1.0 +/- 0.1 x 10(-6) M), a result similar to the inhibition selectivity of human MAO-A. However, trout MAO is less sensitive to clorgyline than is human MAO-A (IC50, 5.8 +/- 0.1 x 10(-10) M). Trout MAO is less sensitive to deprenyl (IC50, 4.6 +/- 0.3 x 10(-7) M) than is human MAO-B (IC50, 1.4 +/- 0.1 x 10(-9) M) when PEA is used as the substrate. These results indicate that trout MAO displays substrate and inhibitor selectivities that are not identical to those of either MAO-A and -B, and it therefore represents a novel type of MAO. The structure of trout MAO will provide insights into the substrate and inhibitor selectivities of the MAOs.
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PMID:Cloning of a novel monoamine oxidase cDNA from trout liver. 780 46


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