title: Caffeinated clues and the promise of adenosine A(2A) antagonists in PD.
abstract: Large prospective epidemiologic studies have linked the consumption of coffee and other caffeinated beverages to a reduced risk of subsequently developing PD. Caffeine as well as more specific antagonists of the adenosine A(2A) receptor have also now been found to attenuate neurotoxicity in a mouse model of PD. The convergence of these epidemiologic and laboratory data supports the possibility that caffeine may reduce the risk of developing PD. However, a neuroprotective effect of caffeine in PD remains unproven; current evidence does not provide a rational basis for recommending caffeine consumption to modify the risk or progression of PD. In addition to possessing neuroprotective potential, caffeine and other A(2A) antagonists have long been known to acutely reverse motor deficits in a variety of PD models. This symptomatic antiparkinsonian benefit of blocking A(2A) receptors, coupled with their remarkably restricted expression in the basal ganglia, have made A(2A) antagonists attractive targets for drug development. Now, with the prospect of a neuroprotective bonus, the novel therapeutic potential of A(2A) antagonists appears all the more promising just as they are entering clinical trials for PD.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, USA. michaels@helix.mgh.harvard.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
mesh_terms: D017668:Age of Onset; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000517:prevention & control*; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D002110:Caffeine