Dual-Target-Directed Drugs that Block Monoamine Oxidase B and Adenosine A(2A) Receptors for Parkinson's Disease

Title

Dual-Target-Directed Drugs that Block Monoamine Oxidase B and Adenosine A(2A) Receptors for Parkinson's Disease

Creator

Petzer J P; Castagnoli N; Schwarzschild M A; Chen J F; Van der Schyf C J

Publisher

Neurotherapeutics

Date

2009
2009-01

Description

Inadequacies of the current pharmacotherapies to treat Parkinson's disease (PD) have prompted efforts to identify novel drug targets. The adenosine A(2A) receptor is one such target. Antagonists of this receptor (A(2A) antagonists) are considered promising agents for the symptomatic treatment of PD. Evidence suggests that A(2A) antagonists may also have neuroprotective properties that may prevent the development of the dyskinesia that often complicates levodopa treatment. Because the therapeutic benefits of A(2A) antagonists are additive to that of dopamine replacement therapy, it may be possible to reduce the dose of the dopaminergic drugs and therefore the occurrence of side effects. Inhibitors of monoamine oxidase (MAO)-B also are considered useful tools for the treatment of PD. When used in combination with levodopa, inhibitors of MAO-B may enhance the elevation of dopamine levels after levodopa treatment, particularly when used in early stages of the disease when dopamine production may not be so severely compromised. Furthermore, MAO-B inhibitors may also possess neuroprotective properties in part by reducing the damaging effect of dopamine turnover in the brain. These effects of MAO-B inhibitors are especially relevant when considering that the brain shows an age-related increase in MAO-B activity. Based on these observations, dual-target-directed drugs, compounds that inhibit MAO-B and antagonize A(2A) receptors, may have value in the management of PD. This review summarizes recent efforts to develop such dual-acting drugs using caffeine as the lead compound.

Subject

adenosine A(2A) receptor; antagonist; caffeine; dopaminergic neurotoxicity; dual-target-directed drug; human-brain; inhibition; istradefylline; l-dopa; mao-b; monoamine-oxidase-b; motor complications; Neurosciences & Neurology; parkinsons-disease; Pharmacology & Pharmacy; rat model; substantia-nigra

Format

Journal Article

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

141-151

Issue

1

Volume

6

Citation

Petzer J P; Castagnoli N; Schwarzschild M A; Chen J F; Van der Schyf C J, “Dual-Target-Directed Drugs that Block Monoamine Oxidase B and Adenosine A(2A) Receptors for Parkinson's Disease,” NEOMED Bibliography Database, accessed September 24, 2021, https://neomed.omeka.net/items/show/6766.

Social Bookmarking