Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease

Author(s): Jacobus P. Petzer, Anel Petzer.

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 8 , 2015

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Abstract:

The current pharmacological therapies for the treatment of Parkinson’s disease are mostly inadequate and recent, improved therapeutic agents are required. Two important molecular targets for the design of anti-parkinsonian therapeutic compounds are the adenosine A2A receptor and the enzyme, monoamine oxidase (MAO) B. Adenosine A2A receptor antagonists are a relatively new class of anti-parkinsonian agents, which act by potentiating dopamine-mediated neurotransmission via dopamine D2 receptors. MAO-B inhibitors are established therapy of Parkinson’s disease and inhibit the MAO-B-catalysed metabolism of dopamine in the brain. This conserves reduced dopamine stores and extends the action of dopamine. A2A antagonism and MAO-B inhibition have also been associated with neuroprotective effects, further establishing roles for these classes of compounds in Parkinson’s disease. Interestingly, caffeine, a known adenosine receptor antagonist, has been recently considered as a lead compound for the design and discovery of A2A antagonists and MAO-B inhibitors. This review summarizes the recent efforts to discover caffeinederived MAO-B inhibitors. The design of caffeine-derived A2A antagonists has been extensively reviewed previously. The prospect of discovering dual-target-directed compounds that act at both targets is also evaluated. Compounds that block the activation and function of both A2A receptors and MAO-B may have a synergistic effect in the treatment of patients with Parkinson’s disease.

Keywords: Adenosine A2A receptor, caffeine, drug design, dual-target-directed, inhibition, monoamine oxidase, Parkinson’s disease.

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Article Details

VOLUME: 22
ISSUE: 8
Year: 2015
Page: [975 - 988]
Pages: 14
DOI: 10.2174/0929867322666141215160015
Price: $58

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