Title:Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease
Volume: 22
Issue: 8
Author(s): Jacobus P. Petzer and Anel Petzer
Affiliation:
Keywords:
Adenosine A2A receptor, caffeine, drug design, dual-target-directed, inhibition, monoamine oxidase, Parkinson’s
disease.
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.
