Clinical chemistry of monoamine oxidase

Glover, Vivette; Sandler, M.

doi:10.1002/cbf.290040203

Cited by 45 publications

(7 citation statements)

References 87 publications

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“…Indeed, at the doses used in our study, chronic treatment with TCP results in a strong and equipotent inhibition of both MAO-A and MAO-B (88 and 93%, respectively) Todd and Baker, 1995), whereas PLZ is slightly more potent in inhibiting MAO-A (MAO-A, 83%; MAO-B, 58%) (Baker et al, 1991), which preferentially deaminates serotonin and norepinephrine (Glover and Sandler, 1986;Fitton et al, 1992). However, because we only used nonselective MAOIs, definitive conclusions regarding the respective role of each subtype of MAO in the reinforcing and motivational properties of nicotine remain to be investigated.…”

Section: Discussionmentioning

confidence: 62%

Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats

Guillem

Vouillac²,

Azar³

et al. 2005

J. Neurosci.

140

121

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Nicotine is the major neuroactive compound of tobacco, which has, by itself, weak reinforcing properties. It is known that levels of the enzymes monoamine oxidase A (MAO-A) and MAO-B are reduced in the platelets and brains of smokers and that substances, other than nicotine, present in tobacco smoke have MAO-inhibitory activities. Here, we report that inhibition of MAO dramatically and specifically increases the motivation to self-administer nicotine in rats. These effects were more prominent in rats selected for high responsiveness to novelty than in rats with low responsiveness to novelty. The results suggest that the inhibition of MAO activity by compounds present in tobacco smoke may combine with nicotine to produce the intense reinforcing properties of cigarette smoking that lead to addiction.

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Section: Discussionmentioning

confidence: 62%

Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats

Guillem

Vouillac²,

Azar³

et al. 2005

J. Neurosci.

140

121

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“…In recent years there has been a resurgence of interest in the search for selective inhibitors of monoamine oxidase type B (MAO-B) for use in Parkinson's disease (Glover and Sandler, 1986;Oreland and Callingham, 1987). This is a consequence of the discovery that the dopamine selective neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) can produce a Parkinson-like syndrome in man and animals and the observation that MAO-B inhibitors afford protection to experimental animals treated with MPTP.…”

Section: Introductionmentioning

confidence: 98%

MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease

Zreika¹,

Fozard²,

Dudley³

et al. 1989

J Neural Transm Gen Sect

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MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC50 = 680 and 3.6 nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED50 values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathomimatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked.

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“…In our preliminary studies a carbohydrazide derivative (1) showed potent inhibition of MAO-A [10]. In order to further enhance anti-depressant properties of such derivatives, a series of hydrazines of type (2 -6), structural variants of the lead molecule (1) and some cyclic derivatives (7 -16) were synthesized in a similar fashion as described earlier [10] and tested for their enzyme inhibitory properties. Monoamine oxidase inhibition was analyzed using rat brain mitochondrial preparation and 5-HT as an enzyme source and substrate, respectively.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of monoamine oxidase–A activity in rat brain by synthetic hydrazines: Structure-activity relationship (SAR)

Dar

Khan

Ateeq

et al. 2005

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A.

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Clinical chemistry of monoamine oxidase

Cited by 45 publications

References 87 publications

Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats

Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats

MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease

Inhibition of monoamine oxidase–A activity in rat brain by synthetic hydrazines: Structure-activity relationship (SAR)

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