Mechanism-based inhibitors of monoamine oxidase

Richards, L. E.; Burger, Alfred

doi:10.1007/978-3-0348-9311-4_7

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…tive deamination reaction with substrates and the suicideinhibition reaction with cyclopropylamine type inhibitors ( Fig. 2A) (Silverman et al 1980;Richards & Burger 1986). While the initial one-electron transfer to the flavin moiety leads to a radical cation (11), subsequent reaction of this species may proceed by several different routes to the iminium ion intermediate (IV) before hydrolysis to yield the product aldehyde.…”

Section: Resultsmentioning

confidence: 99%

Irreversible Inhibition of Rat Liver Mitochondrial MAO A and MAO B by Enantiomers of Deprenyl and α-Methylpargyline

Robinson

Khalil

1995

Journal of Pharmacy and Pharmacology

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Using rat liver mitochondrial monoamine oxidase (MAO) A and MAO B, the possible influence of stereochemical factors upon the irreversible inhibition by propargylamine derivatives has been studied using the enantiomers of deprenyl and of alpha-methylpargyline. Whether studying the inhibition of MAO A or MAO B, little difference was found among enantiomeric pairs in the first-order rate constant (k2) for formation of the enzyme inhibitor adduct. Similarly, and with the exception of (S)-D-(+)-deprenyl (k2 = 0 or an extremely low value at MAO A), the computed value of k2 for the individual enantiomers showed little variation between MAO A and MAO B. These results suggest that inhibitor selectivity towards a particular form of the enzyme is determined predominantly at the competitive phase of the inhibition.

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Section: Resultsmentioning

confidence: 99%

Irreversible Inhibition of Rat Liver Mitochondrial MAO A and MAO B by Enantiomers of Deprenyl and α-Methylpargyline

Robinson

Khalil

1995

Journal of Pharmacy and Pharmacology

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“…Both compounds Nalkylate the reduced flavin prosthetic group of the enzyme (Singer & Salach 1981) possibly via a mechanism involving an intermediate radical cation species (Silverman et a1 1980;Richards & Burger 1986). Both compounds Nalkylate the reduced flavin prosthetic group of the enzyme (Singer & Salach 1981) possibly via a mechanism involving an intermediate radical cation species (Silverman et a1 1980;Richards & Burger 1986).…”

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confidence: 99%

Synthesis, Biological Evaluation and Quantitative Structure Activity Relationship Analysis of Nuclear-substituted Pargylines as Competitive Inhibitors of MAO-A and MAO-B

Ali

Robinson

1991

Journal of Pharmacy and Pharmacology

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A series of nuclear substituted derivatives of pargyline has been prepared and tested (under controlled conditions designed to measure the competitive component of the inhibition) as competitive inhibitors of MAO-A and -B. Adequate correlation of the biological data with the physiochemical constants of substituent groups was obtained only when the m- and p-substituted derivatives were considered separately. Due to the narrow range of activity displayed by the p-substituted derivates when inhibiting MAO-B, meaningful correlations were not found. However, the inhibition of MAO-B by the m-substituted derivatives required the inclusion of the Verloop L parameter for adequate correlation, suggesting that the inhibitor binding site of MAO-B is present within a cavity of more limited lateral dimensions than that present on the MAO-A surface. Inhibition of both MAO-A and -B demonstrated a parabolic relationship between inhibitory activity and pi. Whereas this parabolic relationship showed a maximal value for inhibition of MAO-A (mean pi o = 0.86), inhibition of MAO-B demonstrated a minimal value of pi (pi min = -0.5) i.e. the optimal value of pi for inhibition of MAO-B has not been achieved for this series of compounds but such would be greater than that demonstrated for MAO-A. The Hammett sigma function was important or significant only in the inhibition of MAO-A by the p-substituted derivatives.

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monoamine oxidase inhibitors revisited

Wells

Bjorksten

1989

Can J Anaesth

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Mechanism-based inhibitors of monoamine oxidase

Cited by 4 publications

References 51 publications

Irreversible Inhibition of Rat Liver Mitochondrial MAO A and MAO B by Enantiomers of Deprenyl and α-Methylpargyline

Irreversible Inhibition of Rat Liver Mitochondrial MAO A and MAO B by Enantiomers of Deprenyl and α-Methylpargyline

Synthesis, Biological Evaluation and Quantitative Structure Activity Relationship Analysis of Nuclear-substituted Pargylines as Competitive Inhibitors of MAO-A and MAO-B

monoamine oxidase inhibitors revisited

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