Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease.

Abstract

In the pursuit of improved treatments for Parkinson's disease (PD), the adenosine A(2A) receptor has emerged as an attractive nondopaminergic target. Based on the compelling behavioral pharmacology and selective basal ganglia expression of this G-protein-coupled receptor, its antagonists are now crossing the threshold of clinical development as adjunctive symptomatic treatment for relatively advanced PD. The antiparkinsonian potential of A(2A) antagonism has been boosted further by recent preclinical evidence that A(2A) antagonists might favorably alter the course as well as the symptoms of the disease. Convergent epidemiological and laboratory data have suggested that A(2A) blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. In addition, rodent and nonhuman primate studies have raised the possibility that A(2A) receptor activation contributes to the pathophysiology of dyskinesias-problematic motor complications of standard PD therapy--and that A(2A) antagonism might help prevent them. Realistically, despite being targeted to basal ganglia pathophysiology, A(2A) antagonists may be expected to have other beneficial and adverse effects elsewhere in the central nervous system (e.g., on mood and sleep) and in the periphery (e.g., on immune and inflammatory processes). The thoughtful design of new clinical trials of A(2A) antagonists should take into consideration these counterbalancing hopes and concerns and may do well to shift toward a broader set of disease-modifying as well as symptomatic indications in early PD.

• Authors: Kui Xu, Elena Bastia, Michael Schwarzschild
• Journal: Pharmacology & therapeutics (Pharmacol Ther) Vol. 105 Issue 3 Pg. 267-310 (Mar 2005) ISSN: 0163-7258 [Print] England
• PMID: 15737407 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Adenosine A2 Receptor Antagonists
• Central Nervous System Stimulants
• Purines
• Receptors, Adenosine A2
• istradefylline
• Caffeine

Topics

• Adenosine A2 Receptor Antagonists
• Animals
• Brain (anatomy & histology, drug effects, metabolism)
• Caffeine (therapeutic use)
• Central Nervous System Stimulants (therapeutic use)
• Clinical Trials as Topic
• Humans
• Parkinson Disease (drug therapy, physiopathology, prevention & control)
• Purines (therapeutic use)
• Receptors, Adenosine A2 (physiology)