Monoamine Oxidase Inhibitors
Selegiline
A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.
Monoamine Oxidase
An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.
Dioxanes
Tranylcypromine
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
Phenethylamines
Tyramine
An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems.
Isocarboxazid
Imidazoline Receptors
Desipramine
A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.
Adrenergic Uptake Inhibitors
Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
Species-dependent differences in monoamine oxidase A and B-catalyzed oxidation of various C4 substituted 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridinyl derivatives. (1/92)
In an attempt to provide a better understanding of the scope and limitations of animal models used in some drug development programs and to further our understanding of potential metabolic bioactivation reactions, we have undertaken studies to profile the monoamine oxidase A and B (MAO-A and -B, respectively) activities in liver and brain mitochondrial preparations obtained from a variety of species using a series of 1-methyl-4-aryl-1,2,3, 6-tetrahydropyridinyl substrates. Mitochondrial preparations were incubated with substrates at 37 degrees C in the presence or absence of clorgyline, (R)-deprenyl, or a mixture of these two propargylamines to inhibit MAO-A, MAO-B, or both enzymes. The rates of formation of the corresponding dihydropyridinium metabolites were estimated spectrophotometrically. MAO-B was found to be the principal enzyme present in all tissues. Human liver displayed more MAO-A activity than the liver of any other species studied; subhuman primates displayed little or no detectable MAO-A activity. The properties of the preparations from rat liver were most similar to those from human liver with respect to the MAO-A/MAO-B ratios and the kinetic parameters of the four substrates used to profile enzymatic activity. The kinetic properties of mitochondrial preparations from bovine liver, a commonly used source of purified MAO-B preparations, were consistently different from all of the other species studied. The mitochondrial preparations from rabbit brain and liver also were unusual in that they displayed relatively low MAO activities. Additionally, these enzyme activities were considerably less susceptible to inhibition by clorgyline and (R)-deprenyl. Finally, an exceptionally low MAO-B liver/brain V(max)/K(m) ratio was observed with the mitochondria obtained from the C57BL/6 mouse, an effect that may contribute to the susceptibility of this strain to the toxic effects of the parkinsonian-inducing neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine. (+info)FA-70, a novel selective and irreversible monoamine oxidase-A inhibitor: effect on monoamine metabolism in mouse cerebral cortex. (2/92)
A series of indolealkylamine derivatives has been previously designed and evaluated with the aim of finding the most potent and selective novel monoamine oxidase (MAO) inhibitors to be used in the therapy of neurological and affective disorders. Among them, FA70, a 5-hydroxy-indolealkylamine derivative, has been characterized in vitro as a potent, irreversible, and mechanism-based inhibitor of the MAO-A isoform. The comparison with clorgyline, analyzed under the same experimental conditions, confirmed FA70 as the most potent MAO-A inhibitor. The ex vivo effect of FA70 on MAO activity in mouse cerebral cortex was similar to that observed in vitro, showing more efficacy than in peripheral tissues. The ex vivo effect of FA70 on amine metabolism also was evaluated after acute and chronic treatment, and the results showed that between both MAO isoforms, MAO-A is the only one responsible for monoamine metabolism in this region of the brain. The ex vivo effect of FA70 on dopamine content was correlated with the activation effect on tyrosine hydroxylase activity, the enzyme responsible for the regulation of the limiting step in catecholamine synthesis. (+info)Selective monoamine oxidase subtype inhibition and striatal extracellular dopamine in the guinea-pig. (3/92)
Striatal microdialysate levels of dopamine (DA) in conscious guinea-pigs were measured following acute (1 day) and chronic (21 days) treatment with deprenyl (2 and 0.25 mg kg(-1) s.c., respectively) or clorgyline (4 and 1 mg kg(-1) s.c., respectively), as well as by combination treatment using the same doses of the two inhibitors. These treatments caused selective inhibition of monoamine oxidase type B (MAO-B) or monoamine oxidase type A (MAO-A) respectively. Neither acute nor chronic treatments with deprenyl or clorgyline increased basal or KCl-induced DA levels. Acute and chronic clorgyline treatments were accompanied by significant reductions in striatal microdialysate 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). On the other hand, both acute and chronic deprenyl treatments were accompanied by significant increases in microdialysate HVA with no effect on DOPAC levels. Acute or chronic combined treatment with clorgyline and deprenyl increased tissue but not microdialysate DA levels. The combination treatment given chronically also reduced KCl-induced DA release but enhanced amphetamine-induced DA release. Microdialysate DA levels increased to a smaller extent in guinea-pig than in rat following local striatal infusion of GBR-12909 (100 microM). The difference between guinea-pigs and rats in the response to GBR-12909, could be the result of a lower dopaminergic innervation and/or density of DA transporter. This difference may explain why striatal microdialysate DA levels increased following chronic deprenyl treatment in the rat but not in the guinea-pig. (+info)Phentolamine inhibits exocytosis of glucagon by Gi2 protein-dependent activation of calcineurin in rat pancreatic alpha -cells. (4/92)
Capacitance measurements were used to investigate the molecular mechanisms by which imidazoline compounds inhibit glucagon release in rat pancreatic alpha-cells. The imidazoline compound phentolamine reversibly decreased depolarization-evoked exocytosis >80% without affecting the whole-cell Ca(2+) current. During intracellular application through the recording pipette, phentolamine produced a concentration-dependent decrease in the rate of exocytosis (IC(50) = 9.7 microm). Another imidazoline compound, RX871024, exhibited similar effects on exocytosis (IC(50) = 13 microm). These actions were dependent on activation of pertussis toxin-sensitive G(i2) proteins but were not associated with stimulation of ATP-sensitive K(+) channels or adenylate cyclase activity. The inhibitory effect of phentolamine on exocytosis resulted from activation of the protein phosphatase calcineurin and was abolished by cyclosporin A and deltamethrin. Exocytosis was not affected by intracellular application of specific alpha(2), I(1), and I(2) ligands. Phentolamine reduced glucagon release (IC(50) = 1.2 microm) from intact islets by 40%, an effect abolished by pertussis toxin, cyclosporin A, and deltamethrin. These data suggest that imidazoline compounds inhibit glucagon secretion via G(i2)-dependent activation of calcineurin in the pancreatic alpha-cell. The imidazoline binding site is likely to be localized intracellularly and probably closely associated with the secretory granules. (+info)Substrate and inhibitor specificities for human monoamine oxidase A and B are influenced by a single amino acid. (5/92)
Monoamine oxidase (MAO) is responsible for the oxidation of biogenic and dietary amines. It exists as two isoforms, A and B, which have a 70% amino acid identity and different substrate and inhibitor specificities. This study reports the identification of residues responsible for conferring this specificity in human MAO A and B. Using site-directed mutagenesis we reciprocally interchanged three pairs of corresponding nonconserved amino acids within the central portion of human MAO. Mutant MAO A-I335Y became like MAO B, which exhibits a higher preference for beta-phenylethylamine than for the MAO A preferred substrate serotonin (5-hydroxytryptamine), and became more sensitive to deprenyl (MAO B-specific inhibitor) than to clorgyline (MAO A-specific inhibitor). The reciprocal mutant MAO B-Y326I exhibited an increased preference for 5-hydroxytryptamine, a decreased preference for beta-phenylethylamine, and, similar to MAO A, was more sensitive to clorgyline than to deprenyl. These mutants also showed a distinct shift in sensitivity for the MAO A- and B-selective inhibitors Ro 41-1049 and Ro 16-6491. Mutant pair MAO A-T245I and MAO B-I236T and mutant pair MAO A-D328G and MAO B-G319D reduced catalytic activity but did not alter specificity. Our results indicate that Ile-335 in MAO A and Tyr-326 in MAO B play a critical role in determining substrate and inhibitor specificities in human MAO A and B. (+info)Acute and chronic effects of desipramine and clorgyline on alpha(2)-adrenoceptors regulating noradrenergic transmission in the rat brain: a dual-probe microdialysis study. (6/92)
1. The effects of desipramine (3 mg kg(-1) i.p.) and clorgyline (1 mg kg(-1) i.p.) on extracellular noradrenaline (NA) in the locus coeruleus (LC) and cingulate cortex were assessed in freely-moving rats by dual-probe microdialysis. Functional activities of alpha(2)-adrenoceptors regulating NA release in the LC and cingulate cortex were determined by systemic (0.3 mg kg(-1) i.p.) or local (0.1 - 100 microM) clonidine administration. 2. Extracellular NA was increased in the LC and cingulate cortex following acute desipramine but not clorgyline treatment. Systemic clonidine decreased NA similarly in desipramine-, clorgyline-, and saline-treated animals, in both brain areas. 3. Long-term (twice daily, 14 days) but not short-term (twice daily, 7 days) desipramine, and long-term clorgyline (once daily, 21 days) treatments increased NA (3 fold) in cingulate cortex but not in the LC. Following long-term treatments, responses of NA to systemic clonidine were attenuated in the LC and cingulate cortex. 4. Clonidine perfusion by reverse dialysis into the cingulate cortex decreased local NA (-55 +/- 9%). The effect was attenuated by long-term desipramine (-31 +/- 9%) and clorgyline (-10 +/- 2%) treatments. 5. Clonidine perfusion by reverse dialysis into the LC decreased NA in the LC (-89 +/- 2%) and in cingulate cortex (-52 +/- 12%). This effect was attenuated in the LC following long-term desipramine (-72 +/- 4%) and clorgyline (-62 +/- 12%) treatments but it was not modified in the cingulate cortex (-57 +/- 10% and -68 +/- 6%, respectively). 6. These findings demonstrate that chronic desipramine or clorgyline treatments increase NA in noradrenergic terminal areas and desensitize alpha(2)-adrenoceptors modulating local NA release at somatodendritic and terminal levels. However, somatodendritic alpha(2)-adrenoceptors that control LC firing activity are not desensitized. (+info)Norepinephrine metabolism in neuron: dissociation between 3,4-dihydroxyphenylglycol and 3,4-dihydroxymandelic acid pathways. (7/92)
AIM: To investigate the pre-synaptic metabolism of norepinephrine (NE), judged by variations in plasma concentration of 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxymandelic acid (DOMA). METHODS: Pithed and electrically stimulated (2.5 Hz) rats were given intravenous infusion of exogenous NE (6 nmol . kg-1 . min-1). Plasma NE, DHPG, DOMA, and the activities of mono- amine oxidases (MAO) were measured with the radio-enzymatic assay. RESULTS: Exogenous NE induces an about 100-fold increase in plasma NE concentration while blood pressure remained within normal limits. A 12-fold increase in plasma DHPG and 1.2-fold increase for DOMA were observed. When NE transportation across the pre-synaptic membrane was inhibited by desipramine (2 mg/kg, iv), a great reduction in plasma DHPG concentration (about 25 % of control) was observed while DOMA remained unchanged. When MAO-A activity was inhibited to 25 % of control by clorgyline (2 mg/kg, iv) and MAO-B to 30 % by deprenyl, the plasma DHPG and DOMA concentrations were reduced to 15 % and 70 % of controls, and to 26 % and 76 % of controls, respectively. When clorgyline and deprenyl were combined, plasma DHPG was vanished (less than 2 % of control) while plasma DOMA remained in the same range (72 % of control). CONCLUSION: The metabolizing system of NE in pre-synapse, associating with the pre-synaptic reuptake plus oxidative deamination on the external membrane of mitochondria, is predominant for the reduction to DHPG. (+info)Effects of monoamine oxidase inhibition by clorgyline, deprenil or tranylcypromine on 5-hydroxytryptamine concentrations in rat brain and hyperactivity following subsequent tryptophan administration. (8/92)
1 The effect of various doses of tranylcypromine on the degree of inhibition of rat brain monoamine oxidase (MAO) using 5-hydroxytryptamine (5-HT), dopamine and phenylethylamine as substrates has been examined 120 min after injection of the inhibitor. The concentration of brain 5-HT was also examined both after tranylcypromine alone and also when L-tryptophan (100 mg/kg) had been given 30 min after the tranylcypromine. 2 All doses of tranylcypromine greater than 2.5 mg/kg totally inhibited MAO oxidation of 5-HT, phenylethylamine and dopamine as measured in vitro and produced a similar rise of brain 5-HT in vivo. When tryptophan was also given, there was a further rise of brain 5-HT, which was comparable after all doses of tranylcypromine above 2.5 mg/kg and the characteristic syndrome of hyperactivity made is appearance. 3 Clorgyline (a "Type A" MAO inhibitor), in doses up to 10 mg/kg, did not totally inhibit MAO activity towards phenylethylamine although it did inhibit 5-HT oxidation by 100%. Deprenil (a "Type B" MAO inhibitor) at doses up to 10 mg/kg did not fully inhibit 5-HT oxidation although phenylethylamine oxidation was inhibited almost completely. Administration of either compound alone did not produce as great an accumulation of brain 5-HT as that seen after tranylcypromine (2.5 mg/kg) and subsequent administration of tryptophan did not cause hyperactivity or the rise of brain 5-HT seen after tranylcypromine (2.5 mg/kg) plus tryptophan. 4 Administration of clorgyline plus deprenil (2.5 mg/kg of each) almost totally inhibited oxidation of both 5-HT and phenylethylamine; subsequent tryptophan administration resulted in a rise of brain 5-HT nearly as great as that seen following tranylcypromine (2.5 mg/kg) plus tryptophan and the animals became hyperactive. 5 No evidence was found pointing to the formation of any other 5-substituted indole in the brain following tranylcypromine plus L-tryptophan administration as suggested by others. 6 It is concluded that while 5-HT may normally be metabolized in the brain by "Tye A" MAO in vivo, when this form is inhibited, 5-HT can still be metabolized by "Type B" enzyme. It is only when both forms are almost totally inhibited that the largest rise of brain 5-HT is seen and subsequent tryptophan administration produces the hyperactivity syndrome. (+info)
Pargyline
1998). "Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B ( ... Clorgyline Rasagiline Selegiline Fisar Z, Hroudová J, Raboch J (2010). "Inhibition of monoamine oxidase activity by ...
Monoamine oxidase A
Clorgyline, an MAO-A enzyme inhibitor, prevents apoptosis in melanoma cells, in vitro. Cholangiocarcinoma suppresses MAO-A ... Cimoxatone Clorgyline (irreversible) Methylene Blue Minaprine (Cantor) Moclobemide (Aurorix, Manerix) Phenelzine (Nardil) ...
Clorgiline
... (INN), or clorgyline (BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is ... 1998). "Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B ( ... "The Monoamine Oxidase A Inhibitor Clorgyline Is a Broad-Spectrum Inhibitor of Fungal ABC and MFS Transporter Efflux Pump ...
N-Acetylserotonin
The SSRI fluoxetine and the MAO-A inhibitor clorgyline upregulate AANAT indirectly through serotonergic mechanisms and thereby ... abolishes the hypotensive effects of clorgyline. NAS is produced from serotonin by the enzyme aralkylamine N-acetyltransferase ...
List of MeSH codes (D02)
... clorgyline MeSH D02.092.831.280 - fluoxetine MeSH D02.092.831.500 - mexiletine MeSH D02.092.831.690 - promethazine MeSH D02.092 ...
Monoamine oxidase in pancreatic islets, exocrine pancreas, and liver from rats. Characterization with clorgyline, deprenyl,...
Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium S Lenzen, H Nahrstedt, U Panten ... Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium S Lenzen et al. Naunyn Schmiedebergs Arch ... Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue ... Using the same three MAO substrates and compared with the effects of the selective enzyme inhibitors, clorgyline and deprenyl, ...
Monoamine oxidase in pancreatic islets, exocrine pancreas, and liver from rats. Characterization with clorgyline, deprenyl,...
Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium S Lenzen, H Nahrstedt, U Panten ... Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium S Lenzen et al. Naunyn Schmiedebergs Arch ... Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue ... Using the same three MAO substrates and compared with the effects of the selective enzyme inhibitors, clorgyline and deprenyl, ...
Clorgyline-mediated reversal of neurological deficits in a Complexin 2 knockout mouse - Sheffield Hallam University Research...
For example, clorgyline-treated Cplx2-/- mice spent significantly more time interacting with a novel visitor mouse compared to ... Chronic treatment with clorgyline, an irreversible inhibitor of monoamine oxidase A, restored hippocampal noradrenaline to ... Clorgyline-mediated reversal of neurological deficits in a Complexin 2 knockout mouse ... Clorgyline-mediated reversal of neurological deficits in a Complexin 2 knockout mouse. Human Molecular Genetics, 19 (17), 3402- ...
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Biomarkers Search
MeSH Browser
Clorgyline Preferred Term Term UI T008748. Date01/01/1999. LexicalTag NON. ThesaurusID ... Clorgyline Preferred Concept UI. M0004631. Registry Number. LYJ16FZU9Q. Related Numbers. 17780-72-2. Scope Note. An ... Clorgyline. Tree Number(s). D02.092.831.180. Unique ID. D003010. RDF Unique Identifier. http://id.nlm.nih.gov/mesh/D003010 ...
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MeSH Browser
Clorgyline Preferred Term Term UI T008748. Date01/01/1999. LexicalTag NON. ThesaurusID ... Clorgyline Preferred Concept UI. M0004631. Registry Number. LYJ16FZU9Q. Related Numbers. 17780-72-2. Scope Note. An ... Clorgyline. Tree Number(s). D02.092.831.180. Unique ID. D003010. RDF Unique Identifier. http://id.nlm.nih.gov/mesh/D003010 ...
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DeCS
Clorgyline-Resistant Amine Oxidase Entry term(s). Amine Oxidase, Clorgyline-Resistant Clorgyline Resistant Amine Oxidase ... Amine Oxidase, Clorgyline-Resistant. Clorgyline Resistant Amine Oxidase. Clorgyline-Resistant Amine Oxidase. Oxidase, ... Clorgyline-Resistant Amine Oxidase - Narrower Concept UI. M0002390. Preferred term. ...
Publications - National Institute of Chemistry
Isocarboxazid drug class
Selective and Nonselective Monoamine Oxidase Inhibitors: Behavioral Disturbances During Their Administration to Depressed...
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American Journal of PharmTech Research
NDF-RT Code NDF-RT Name
Fasciolíase/parasitologia
2014 - PRISM | University of Saskatchewan
"Role of monoamine oxidases in the exaggerated 5-hydroxytryptamine-indu" by Sai Wang Seto, Ho Yeung Lam et al.
The Unsilenced Science: Scientists Rediscover the Violence Gene, MAOA-2R
ABORTIFACIENT AGENTS ABORTIFACIENT AGENTS
ENZYME INHIBITORS CLORGYLINE ENZYME INHIBITORS COFORMYCIN ENZYME INHIBITORS COUMAPHOS ENZYME INHIBITORS CUPRIZONE ENZYME ... MONOAMINE OXIDASE INHIBITORS CLORGYLINE MONOAMINE OXIDASE INHIBITORS CUPRIZONE MONOAMINE OXIDASE INHIBITORS FURAZOLIDONE ... PSYCHOTROPIC DRUGS CLORGYLINE PSYCHOTROPIC DRUGS CLOZAPINE PSYCHOTROPIC DRUGS DEANOL PSYCHOTROPIC DRUGS DESIPRAMINE ... ANTIDEPRESSIVE AGENTS CLORGYLINE ANTIDEPRESSIVE AGENTS DEANOL ANTIDEPRESSIVE AGENTS DESIPRAMINE ANTIDEPRESSIVE AGENTS DOTHIEPIN ...
Division of AIDS Anti-HIV/OI/TB Therapeutics Database - Surveillance Memo
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Comparative analysis of the neurochemical profile and MAO inhibition properties of N-(furan-2-ylmethyl)-N-methylprop-2-yn-1...
Inhibitor2
- Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue homogenates, while deprenyl, a selective inhibitor of MAO-B, preferentially inhibited deamination of phenylethylamine. (nih.gov)
- The enhanced component of 5-HT-induced tension development was eradicated by clorgyline (a MAO-A inhibitor). (edu.hk)
Monoamine oxidase2
Phenelzine1
- 14. The MAO inhibitors phenelzine and clorgyline revert enzalutamide resistance in castration resistant prostate cancer. (nih.gov)