Interactions of Nitrogen-Containing Xenobiotics with Monoamine Oxidase (MAO) Isozymes A and B:  SAR Studies on MAO Substrates and Inhibitors

Kalgutkar, Amit S.; Dalvie, Deepak; Castagnoli, Neal; Taylor, Timothy J.

doi:10.1021/tx010073b

Cited by 197 publications

(96 citation statements)

References 244 publications

(332 reference statements)

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“…Monoamine oxidase-A (MAO-A) shows greater activity towards deamination of serotonin and norepinephrine, while MAO-B shows greater activity towards benzylamine and phenylethylamine [3]. They are equally active towards dopamine and tyramine.…”

Section: Monoamine Oxidase-b (Mao-b) Inhibitorsmentioning

confidence: 99%

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

Robakis

Fahn

2015

CNS Drugs

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Inhibitors of monoamine oxidase-B (MAO-B) occupy an important place in the treatment of Parkinson's disease. Selegiline was the first MAO-B to be used therapeutically, while rasagiline is a second-generation drug with higher potency and selectivity. Safinamide is an investigational MAO-B inhibitor with non-dopaminergic properties that may provide advantages over its predecessors. As a class, MAO-B inhibitors are safe and well tolerated and provide symptomatic benefit both as monotherapy and in combination with other antiparkinsonian medications from early to late stages of disease. In combination with levodopa, MAO-B inhibitors may improve motor fluctuations and allow for lower total doses of levodopa. Patient characteristics and preferences can be important factors in deciding between agents. As a class, MAO-B inhibitors have shown promise as disease-modifying agents, but the clinical trial evidence to date has not been strong enough to afford them such a label. Future research may help further elucidate their relative merits and clarify their role in altering disease progression. Key PointsRasagiline and selegiline are two monoamine oxidase-B (MAO-B) inhibitors commonly used in the treatment of Parkinson's disease (PD), while safinamide is an investigational agent of the same class.MAO-B inhibitors are safe, with few serious side effects, and provide mild but worthwhile improvements in the motor symptoms of PD, either as monotherapy or adjunctive to levodopa.The possibility that MAO-B inhibitors could slow down the progression of PD has been suggested by some studies but not by others and remains an open question.

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Section: Monoamine Oxidase-b (Mao-b) Inhibitorsmentioning

confidence: 99%

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

Robakis

Fahn

2015

CNS Drugs

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“…They are located in the mitochondrial outer membranes of neuronal, glial, and other cells particularly abundant in the liver and brain [1,2]. These FAD-dependent enzymes catalyze the oxidative deamination of several endogenous and exogenous monoamines and are responsible for the regulation and metabolism of major monoamine neurotransmitters, such as serotonin (5-OH tryptamine), noradrenaline, and dopamine [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we have demonstrated a series of 3-benzyl-2-substituted quinoxalines as selective MAO-A inhibitors bearing substituted amino or hydrazino functionalities at position 2 [7] and novel structural variants of [1,2,4]triazolo [4,3-a]quinoxaline derivatives [8]. In addition, substituted pyridazine-1-yl acetic acid derivatives [9], and α-ketoamino acid ester derivatives [10] were established as selective monoamine oxidase-A inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors

et al. 2015

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Three series of 4,6-dimethoxy-, 4,6-dipiperidino-and 4,6-dimorpholino-1,3,5-triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity.

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“…30 In mammals, two distinct isoforms of MAO are present in most tissues, As such, the development of synthetic methodologies that combine high levels of regiocontrol and flexibility continues to be intensively researched within organic chemistry.…”

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confidence: 99%