Inhibition of semicarbazide-sensitive amine oxidase by monoamine oxidase B inhibitors from the oxazolidinone series

Dostert, P.; Guffroy, C.; Benedetti, Μ. Strolin; Boucher, Thierry

doi:10.1111/j.2042-7158.1984.tb04875.x

Cited by 10 publications

(2 citation statements)

References 10 publications

(3 reference statements)

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“…The SSAO inhibitory properties of several 5-aminomethyl-3-aryl derivatives were also investigated (Fig. 6) [76]. Of the four compounds tested, the most potent inhibitor of SSAO is MDL 220662 with a micromolar IC 50 in rat heart and aorta.…”

Section: Oxazolidinone Derivativesmentioning

confidence: 99%

Semicarbazide-Sensitive Amine Oxidase: Current Status and Perspectives

Mátyus¹,

Dajka-Halasz²,

Foldi³

et al. 2004

CMC

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Semicarbazide-sensitive amine-oxidase (SSAO) is present in various human tissues and in plasma. Oxidative deamination of short-chain aliphatic amines is catalyzed by this enzyme to afford the corresponding aldehydes, ammonia and hydrogen peroxide. Methylamine and aminoacetone have been recognized to be physiological substrates for SSAO. There are several pathological states where increased serum SSAO activity have been found, such as diabetes mellitus, congestive heart failure, multiple types of cerebral infarction, uraemia, and hepatic cirrhosis. The role of SSAO in pathophysiology of diabetes has been most extensively investigated. The elevated formation of the potentially cytotoxic products of the enzyme may contribute to the endothelial injury of blood vessels, resulting in the early development of severe atherosclerosis; it may also contribute to the pathogenesis of diabetic angiopathy. It is now suggested that SSAO inhibitors may prevent the development of atherosclerosis and diabetic complications as well. Inhibitors can be conveniently subdivided into the main groups of hydrazine derivatives, arylalkylamines, propenyl- and propargylamines, oxazolidinones, and haloalkylamines. Of them, aryl(alkyl)hydrazines, and 3-halo-2-phenylallylamines are generally very strong SSAO inhibitors. Most of these inhibitors of SSAO have been originally developed for other purposes, or they are simple chemical reagents with highly reactive structural element(s); these compounds have not been able to fulfil all criteria of high potency, selectivity, and acceptable toxicity. New potent compounds with selectivity and low toxicity are needed, which may prove useful tools for understanding the roles and function of SSAO, or they may even be valuable substances for treatment of various diseases.

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Section: Oxazolidinone Derivativesmentioning

confidence: 99%

Semicarbazide-Sensitive Amine Oxidase: Current Status and Perspectives

Mátyus¹,

Dajka-Halasz²,

Foldi³

et al. 2004

CMC

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“…Mixed irreversible inhibitors (phenelzine, tranylcypromine, isocarboxazid and nialamide), irreversible MAO B inhibitors (selegiline, rasagiline and pargyline) and reversible MAO A inhibitors (moclobemide and toloxatone) are in clinical use. Although interesting non‐hydrazine inhibitors of semicarbazide‐sensitive AO (SSAO) have been described in the past, including oxazolidinone derivatives [18], SSAOs were not important targets for inhibition. Recently, as altered levels of SSAO have been found in some disease states [15,19–22] (see ), it has been recognized that SSAO inhibitors might have potential therapeutic value.…”

Section: Factors Affecting the Relative Importance Of Amine Oxidases mentioning

confidence: 99%

Amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans: has the involvement of amine oxidases been neglected?

Benedetti

Tipton

Whomsley

2007

Fundamemntal Clinical Pharma

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In this review, the major enzyme systems involved in vivo in the oxidative metabolism of xenobiotic amines in humans are discussed, i.e. the monooxygenases [cytochrome P450 system (CYPs) and flavin-containing monooxygenases (FMOs)] and the amine oxidases (AOs). Concerning the metabolism of xenobiotic amines (drugs in particular) by monoamine oxidases (MAOs), this aspect has been largely neglected in the past. An exception is the extensive investigation carried out on the inhibition of the metabolism of tyramine, when tyramine-containing food is ingested by subjects taking inhibitors of MAO A or of both MAO A and B. Moreover, investigations in humans on the metabolism of drug amines on the market by AOs, such as semicarbazide-sensitive amine oxidases (SSAOs) and polyamine oxidases (PAOs), are practically nonexistent, with the exception of amlodipine. In contrast to MAOs, monooxygenases (CYP isoenzymes more than FMOs) have been extensively investigated concerning their involvement in the metabolism of xenobiotics. It is possible that the contribution of AOs to the overall metabolism of xenobiotic amines in humans is underestimated or erroneously estimated, as most investigations of drug metabolism are performed using in vitro test systems optimized for CYP activity, such as liver microsomes, and most investigations of drug metabolism in vivo in humans carry out only the identification of the final, stable metabolites. However, for some drugs on the market, the involvement of MAOs in their in vivo metabolism in humans has been demonstrated recently, among these drugs citalopram, sertraline and the triptans are examples that can be mentioned.

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Some pharmacological and clinical aspects of reversible MAO inhibitors

Benedetti

1984

IUPHAR 9th International Congress of Pharmacology

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Inhibition of semicarbazide-sensitive amine oxidase by monoamine oxidase B inhibitors from the oxazolidinone series

Cited by 10 publications

References 10 publications

Semicarbazide-Sensitive Amine Oxidase: Current Status and Perspectives

Semicarbazide-Sensitive Amine Oxidase: Current Status and Perspectives

Amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans: has the involvement of amine oxidases been neglected?

Some pharmacological and clinical aspects of reversible MAO inhibitors

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