Type-B monoamine oxidase

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

J. Wouters, Rational approaches towards reversible inhibition of type B monoamine oxidase. Design and evaluation of a novel 5H-indeno[1,2-c]pyridazin-5-one derivative, Bioorg. Med. Chem. Lett. 13 (2003) 69-73. 

Carrieri, A., Carotti, A. Barreca, M.L., Al-tomare, C. Binding Models of Reversible Inhibitors to Type-B Monoamine Oxidase. J. Comput.-Aided Mol. Des. 2002,... 

Increased Dopamine Turnover. Dopamine is normally stored in vesicles, where it is nonreactive. However, when released into the cytosol, it is metabolized in the mitochondria, primarily by type B monoamine oxidase (MAOb) to... 

Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979 35 1283-1284. 

Carrieri A, Carotti A, Barreca ML, Altomare C. Binding models of reversible inhibitors to type-B monoamine oxidase. J Comput Aided Mol Des 2002 16 769-78. 

Green AL (1981) The kinetics of inhibition of type-B monoamine oxidase by cloryline, pargyline, and (-) deprenyl. J Pharm Pharmacol 33 798-800... 

R.W. Fuller, S.K. Hemrick-Luecke, B.B. Molloy, A/-[(2-o-lndophenoxy)ethyl]cyclopro-pylamine hydrochloride (LY121768), a potent and selective irreversible inhibitor of type A monoamine oxidase, Biochem. Pharmacol. 32 (1983) 1243-1249. 

There are two types of MAO MAO-A and MAO-B. Monoamine oxidase A preferentially deaminates norepinephrine and serotonin, while MAO-B prefer-... 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

There are two types of monoamine oxidase (i.e., A and B), which represent different proteins. MAO-A preferentially deaminates serotonin and NE, whereas MAO-B preferentially deaminates dopamine, benzylamine, and phenylethylamine. Certain substrates (e.g., tyramine and tryptamine) are comparably deaminated by both types. 

Monoamine oxidases are flavoproteins that contain one molecule of FAD per molecule. There are two major types of monoamine oxidase (A and B), whose relative concentration varies in tissues of the same species. In general, the A form of the enzyme is more active with endogenous neurotransmitter amines (serotonin, norepinephrine, and epinephrine), whereas the B form is more active toward xenobiotic amines such as 2-phenethylamine. 

Strolin Benedetti M, Keane PE (1980) Differential changes in monoamine oxidase A and B activity in the aging brain. J Neurochem 35 1026-1032 Student AK, Edwards DJ (1977) Subcellular localization of types A and B monoamine oxidase in rat brain. Biochem Pharm 26 2337-2342 Tanner CM, Goldmann SM (1996) Epidemiology of Parkinson s disease. Neurol Clin 14 317-335... 

Researchers have discovered that there are two types of monoamine oxidase enzyme MAO-A and MAO-B, each located in different regions of the body. Older MAOIs, such as Nardil, inhibit both versions of monoamine oxidase, resulting in increased serotonin and norepinephrine inside the cell (and also leakage into the synapse, thus activating receptors). Increases in serotonin and noreinephrine receptor activation can lead to several over-stimulating side effects. These central nervous system effects include tremors, insomnia, agitation, and occasionally, precipitation of a mania in patients with bipolar depression. 

Fig. 37.3. Major metabolic pathways of histamine, from intradermal histamine as measured in the urine in 12 hours in human males (5). HMT, histamine N-methyltransferase MAO-B, monoamine oxidase type B DAO, diamineoxidase ALDH, aldehyde dehydrogenase ADO, aldehyde oxidase XO, xanthine oxidase PRT, phosphoribosyl transferase.

The antidepressant activity of hypericum has been extensively investigated over the last two decades in animal models (forced-swimming and tail-suspension tests) as well as in humans. Clinical trials have demonstrated an improvement in symptoms of anxiety, dysphoric mood, hypersomnia, anorexia, depression, insomnia, psychomotor retardation, and other subjective indicators.Potential for the treatment of premenstrual syndrome (PMS) also exists. Earlier studies also showed that hypericum enhanced mice exploratory activity in a foreign environment, extended narcotic sleeping time (dose dependent), is a reserpine antagonist, and decreased aggression in socially isolated male mice. Hypericin has been found to inhibit in vitro almost irreversibly both type A and B monoamine oxidase (MAO) in rat brain mitochondria. Type A MAO (serotonin) inhibition was more pronounced, but with long-term use (8 weeks of daily treatment). Other mechanisms of action, such as serotonin transport and up-... 

The beneficial effect of deprenyl in Parkinson s disease was su ested to be in part due to its effect on increasing the levels of SOD activity in several brain regions (Carrillo et al., 1993). Deprenyl is known to inhibit monoamine oxidase type B, which results in a reduction in hydrogen peroxide formation by blockade of the oxidative deamination of dopamine. That is believed to be the major mechanism of action of this drug in inhibiting the progression of Parkinson s disease. 

MAOI non-selective monoamine oxidase (A/B) inhibitors RIMA reversible inhibitor of monamine oxidase type A SSRI selective serotonin (5-HT) reuptake inhibitors SNRI serotonin/noradrenaline reuptake inhibitor SNARI selective noradrenaline (NA) reuptake inhibitor NA = 5-HT — DA potency of the drug is very similar in raising the level of both (or all three) monamines NA > 5-HT more selective for NA 5-HT>NA more selective for 5-HT NA increases the release of NA. 

Which of the following is a selective inhibitor of monoamine oxidase type B (MAO-B) and, therefore, useful in treating parkinsonism ... 

Monoamine oxidase type B activity is increased / Glutamate pathways of the cortex and limbic structures are abnormal... 

Fowler CJ, Mantle TJ, Tipton KF. The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, 1-deprenyl and pargyline. Biochem Pharmacol 1982 31(22) 3555-3561. 

Pharmacology Selegiline hydrochloride is a levorotatory acetylenic derivative of phenethylamine. Although the mechanism of action is not fully understood, inhibition of monoamine oxidase (MAO) type B activity is of primary importance and selegiline... 

Monoamine oxidase (MAO) inhibitors block the oxidative deamination of monoamines, i.e. norepinephrine and serotonin by inhibiting monoamine oxidase type A (MAO-A) and dopamine also by monoamine oxidase type B (MAO-B) inhibition, thereby increasing these neurotransmittors at their receptors in the brain and in the periphery. MAO-A... 

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