title: Caffeine as a lead compound for the design of therapeutic agents for the treatment of 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.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. jacques.petzer@nwu.ac.za.
authors.forename: Anel
authors.initials: A
authors.lastname: Petzer
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D008996:Monoamine Oxidase Inhibitors; D002110:Caffeine; D008995:Monoamine Oxidase