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

摘要

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 A(2A) receptor and the enzyme, monoamine oxidase (MAO) B. Adenosine A(2A) receptor antagonists are a relatively new class of anti-parkinsonian agents, which act by potentiating dopamine-mediated neurotransmission via dopamine D-2 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. A(2A) 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 A(2A) antagonists and MAO-B inhibitors. This review summarizes the recent efforts to discover caffeine-derived MAO-B inhibitors. The design of caffeine-derived A(2A) 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 A(2A) receptors and MAO-B may have a synergistic effect in the treatment of patients with Parkinson's disease.