Monoamine oxidase B MAO

Hou WC, Lin RD, Chen CT, Lee MH. Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla. J Ethnopharmacol 2005 100 216-220. 

HA turnover is rapid in the brain, with a half-life of about 30 min. This can change very quickly depending on neuronal activity. There is no high-affinity uptake system for HA once released, HA is inactivated by catabolism. In the brain, released HA is methylated almost exclusively by the enzyme histamine-N-methyltransferase (E.C. 2.1.1.8). The tele-methyl-HA is subsequently degraded by monoamine oxidase-B (MAO-B) and aldehyde dehydrogenase to produce tele-methylimidazoleacetic acid (Brown et ah, 2001). 

Fowler, J., Volkow, N., Wang, G. et al. Neuropharmacological actions of cigarette smoke brain monoamine oxidase B (MAO B) inhibition. J. Addictive Dis. 17 23, 1998. 

Monotherapy usually begins with a monoamine oxidase-B (MAO-B) inhibitor, or if the patient is physiologically young, a dopamine agonist. 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

Selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B) as long as it is... 

Monoamine oxidase A (MAO A) acts selectively on the substrates norepinephrine and serotonin, whereas monoamine oxidase B (MAO B) preferentially affects phenylethylamine. Both MAO A and MAO B oxidize dopamine and tyramine. MAO A inhibition appears to be most relevant to the antidepressant effects of these drugs. Drugs that inhibit both MAO A and MAO B are called non-selective. The MAOI antidepressants currently available in the United States are nonselective inhibitors. Because tyramine can be metabolized by either MAO A or MAO B, drugs that selectively inhibit one of these enzymes but not the other do not require dietary... 

Another approach to the therapy of Parkinson s disease involves the use of enzyme inhibitors. For example, inhibition of the enzyme monoamine oxidase B (MAO-B) by selegiline (4.105) improves the duration of L-DOPA therapy because it inhibits the breakdown of dopamine but not of NE. Likewise, inhibitors of catechol-O-methyl-transferase (COMT) can also be exploited as agents for the treatment of Parkinson s disease. L-DOPA and dopamine become inactivated by methylation the COMT enzyme responsible for this metabolic transformation can be clocked by agents such as entacapone (4.106) or tolcapone (4.107), allowing higher levels of L-DOPA and dopamine to be achieved in the corpus striamm of the brain. 

Fig. (2). Hypothesized mechanisms of neurotoxicity of MPTP. After injection of MPTP, its native form crosses the blood brain barrier (BBB) and is oxidized by monoamine oxidase B (MAO-B) into MPP+. This metabolite is transported and concentrated into nigrostriatal dopamine and exerts a neurotoxic effect...

In 1982 a number of young people in California injected themselves with an illegally manufactured opiate drug that was subsequently found contaminated with N-methyl-4-phenyltetrahydropyridine (MPTP). Within a few days they developed irreversible symptoms of Parkinson disease. Subsequent investigation revealed that MPTP itself is not toxic but that it is oxidized by monoamine oxidase B (MAO-B) to the corresponding pyridinium derivative MPP+ (Eq. 30-4). It is this pyridinium derivative, or perhaps... 

The free phenols that are produced in the brain (when they break off during the reaction with AChE), are related to the drug selegiline (Fig. 12.8), which is a monoamine oxidase B (MAO-B) inhibitor, so that they also exhibit such inhibitory activity. MAO-B inhibitors are helpful in Parkinson s disease, mainly because they cause an increase in the level of dopamine, and are also antidepressants. These compounds are currently under investigation as treatment for Alzheimer s disease complicated by other cognitive deficits. 

Inhibitors of monoamine oxidase-B (MAO ). Monoamine oxidase occurs in the form of two isozymes MAOa and MAOB. The corpus striatumis rich in MAOB. This isozyme can be inhibited by selegiline. Degradation of biogenic amines in peripheral organs is not affected because MAOa remains functional. 

NMDA receptor modulators (47-50)], monoamine oxidase B (MAO B) inhibitors (51-55), antioxidants (52, 56-59), nootropics (41, 60), lipid-lowering agents (e.g., statins) (61), insulin (62), anti-inflammatory agents (63-67), and estrogen supplementation (63, 65, 66, 68, 69). Because several other reviews are available that compare these therapeutic approaches (70-77), the remainder of the present chapter focuses on ion channel modulation approaches to cognition enhancement. 

Monoamine oxidase B (MAO-B) is a membrane-bound flavoprotein that catalyzes the two-electron oxidation of primary, secondary, and tertiary amines with a preference for primary amines. Extensive studies have addressed the issue of whether the hydrogen transfer occurs via a step-wise mechanism (i.e. electron transfer followed by H+) or a concerted process (H ) (e.g. Refs. 103, 104). 

Inhibition of monoamine oxidase B (MAO-B) was observed in rat brain homogenates treated with an extract of Brown s lily (L. brownii var. colchesteri) with an ICgg value of 0.40 mg/ ml (Lin et al. 2003). 

In 2005, the inhibition of monoamine oxidase B (MAO-B) of a phenethylamine selective metabolism enzyme or dopamine selective metabolism enzyme by (-)-epicatechin (1) was examined. Because, it could be expected that the attenuation of monoamine oxidase B (MAO-B) activity might provide the protection against the oxidative neurodegeneration. Actually, the inhibition of monoamine oxidase B (MAO-B) activity has been used as part of the treatment of Parkinson s and Alzheimer s patients. 

First, (-)-epicatechin (1) could inhibit monoamine oxidase B (MAO-B) by an assay of rat brain monoamine oxidase B (MAO-B). The 50% inhibitory concentration (IC50) value of (-)-epicatechin (1) was 58.9 aM, and the inhibition occurred in a dose-dependent manner by the fluorescence method. 

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