Rasagiline mesylate is an irreversible MAO-B inhibitor which requires daily oral administration for treatment of Parkinson's disease due to its short half-life.
MAO-B-specific inhibitors such as some of the quinazolinone compounds investigated here may act as leads for the design of therapies for neurodegenerative disorders such as Parkinson's disease.
The irreversible monoamine oxidase B (MAO B) inhibitor rasagiline has been described with multiple disease modifying effects in vitro on models of Parkinson's disease.
Here, we aimed to explore the antidepressant-like effects of propargyl MAO-B inhibitors, selegiline and rasagiline, in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD model, and to elucidate the mechanisms underlying these effects.
The current pharmacological treatments for Parkinson's disease only offer symptomatic relief to the patients and are based on the administration of levodopa and catechol-O-methyltransferase or monoamine oxidase-B inhibitors (IMAO-B).
<b>:</b> Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn<sup>3+</sup>) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, proteasome inhibition, and selective DA neuron vulnerability, which is implicated in the pathogenesis of Parkinson's disease (PD).
MAO-B specific inhibitors such as those discovered here may be of interest in the treatment of neurodegenerative disorders such as Parkinson's disease.
<b>Introduction</b>: Selective monoamine oxidase-B (MAO-B) inhibitors are currently used as coadjuvants for the treatment of early motor symptoms in Parkinson's disease.
Discovery of coumarin Mannich base derivatives as multifunctional agents against monoamine oxidase B and neuroinflammation for the treatment of Parkinson's disease.
Good potency MAO-B inhibitors may act as leads for the design and development of therapy for Parkinson's disease where these agents reduce the central metabolism of dopamine.
Selegiline, an irreversible inhibitor of monoamine oxidase (MAO)-type B, is widely prescribed for Parkinson's disease and, at higher doses, for major and atypical depression, whereby it is non-selectively inhibitory to both MAO-A and MAO-B activities.
Thus, phenylisoxazole carbohydrazides can be promising leads in the development of potent, selective and reversible MAO-B inhibitors for the treatment of Parkinson's disease.
In addition to the symptomatic benefits offered by MAO-B inhibitors, these drugs may also possess neuroprotective properties and possibly delay the progression of Parkinson's disease.
Monoamine oxidase type B inhibitors act in Parkinson's disease (PD) via potentiation of dopamine, but may also have neuroprotective effects by reducing oxidative damage.