The Dramballet Studio

Belova, E. N.

doi:10.1163/2211730x96x00144

Cited by 10 publications

(1 citation statement)

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“…The only current drug marketed for reversible inhibition of MAO A is moclobemide [ 65 ]. The anti-bacterial drug linezolid is a weak inhibitor [ 66 ], but many other oxazolidinones are potent reversible inhibitors of MAO [ 67 , 68 ], including the MAO-A selective inhibitor befloxatone [ 69 ]. The need to avoid inhibiting MAO A in the gut and the increase of MAO B in ageing brain has driven the search for potent reversible inhibitors of MAO B. Safinamide, an anticonvulsant now marketed for Parkinson’s disease, is an inhibitor of MAO B that is effective at nanomolar concentrations [ 70 ].…”

Section: Inhibition Of Neurotransmitter Breakdown In Neurodegeneramentioning

confidence: 99%

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

2017

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The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

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Section: Inhibition Of Neurotransmitter Breakdown In Neurodegeneramentioning

confidence: 99%

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

2017

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Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions

Rendić¹,

Crouch

Guengerich

2022

Arch Toxicol

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This is an overview of the metabolic reactions of drugs, natural products, physiological compounds, and other (general) chemicals catalyzed by flavin monooxygenase (FMO), monoamine oxidase (MAO), NAD(P)H quinone oxidoreductase (NQO), and molybdenum hydroxylase enzymes (aldehyde oxidase (AOX) and xanthine oxidoreductase (XOR)), including roles as substrates, inducers, and inhibitors of the enzymes. The metabolism and bioactivation of selected examples of each group (i.e., drugs, “general chemicals,” natural products, and physiological compounds) are discussed. We identified a higher fraction of bioactivation reactions for FMO enzymes compared to other enzymes, predominately involving drugs and general chemicals. With MAO enzymes, physiological compounds predominate as substrates, and some products lead to unwanted side effects or illness. AOX and XOR enzymes are molybdenum hydroxylases that catalyze the oxidation of various heteroaromatic rings and aldehydes and the reduction of a number of different functional groups. While neither of these two enzymes contributes substantially to the metabolism of currently marketed drugs, AOX has become a frequently encountered route of metabolism among drug discovery programs in the past 10–15 years. XOR has even less of a role in the metabolism of clinical drugs and preclinical drug candidates than AOX, likely due to narrower substrate specificity.

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Behavioural profiles of the reversible monoamine-oxidase-A inhibitors befloxatone and moclobemide in an experimental model for screening anxiolytic and anti-panic drugs

Perrault

Sanger

1997

Psychopharmacology

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The present study compared the behavioural effects of acute and chronic (one daily i.p. injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) and befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDTB) which has been designed for screening anxiolytic and anti-panic drugs. In the MDTB, Swiss mice were confronted with a natural threat (a rat) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flight, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behaviours were observed. This was in contrast to chronic treatments, where moclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a significant reduction in one flight measure (avoidance distance when the rat was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but not moclobemide, increased RA responses when mice were constrained in one part of the apparatus facing the rat, which remained at a constant distance. No other drug effects were observed with either compound. Although these behavioural profiles are consistent with an anxiolytic-like effect, the finding of an action upon a limited number of defence responses suggests a weaker anxiolytic-like potential compared to that of classical anxiolytics. However, in view of previous data with panic-modulating compounds on flight behaviours in the MDTB, the present results are in line with clinical results showing that moclobemide is effective in panic disorders and suggest that befloxatone may have some efficacy in the clinical management of panic.

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The Dramballet Studio

Cited by 10 publications

References 0 publications

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions

Behavioural profiles of the reversible monoamine-oxidase-A inhibitors befloxatone and moclobemide in an experimental model for screening anxiolytic and anti-panic drugs

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