Title:Synthetic and Natural Monoamine Oxidase Inhibitors as Potential Lead Compounds for Effective Therapeutics
Volume: 16
Issue: 2
Author(s): Ashish Pathak, Amit K. Srivastava, Pradeep K. Singour and Panchanan Gouda
Affiliation:
Keywords:
Monoamine oxidase inhibitors, neurotransmitters, parkinson’s, depression, flavonoids, coumarins, xanthones,
therapeutics.
Abstract: Monoamine oxidases A and B (MAO-A and B) play a critical role in the metabolism of intracellular
neurotransmitters of the central nervous system. For decades, MAO inhibitors have proven
their clinical efficacy as potential drug targets for several neurological and neurodegenerative diseases.
Use of first generation non selective MAO inhibitors as neuropsychiatric drugs elicited several side effects
like hypertensive crisis and cheese reaction. Therefore their use is now limited due to non-selectivity towards MAO
isoforms and inhibition of metabolizing enzymes like cytochrome P450. Development of selective and specific MAO inhibitors
like moclobemide, toloxatone improves their efficacy as disease-modifying effects in monotherapy as well as adjunctive
therapy. Recently a lot of research has been done to elucidate the pharmacological potential of medicinal plants
and their isolated bioactive constituents having MAO inhibitory activity. Herbs containing MAO inhibitors are extensively
used for the development of potent synthetic drugs and as safe and effective alternatives to the available synthetic
drugs in the treatment of neurodegenerative diseases such as depression, Parkinson and Alzheimer’s. In several diseases
like Parkinson natural MAO inhibitors prevented the neuron denaturalization by their dual action via enhancing neurotransmission
of dopamine as well as lowering the generation of free radicals and toxins. Currently development of selective
MAO inhibitors is still under study to achieve more effective therapies by using Computer Aided Drug Designing,
Ligand-based models and structure-activity hypothesis. These approaches also facilitate understanding the interaction of
newly designed molecule with MAO enzymes and the rationalization of probable mechanisms of action.
