Potential role of adenosine antagonist therapy in pathological tremor disorders

The continuing lack of effective long-term therapies for Parkinson's disease and other disorders in which a primary symptom is involuntary tremor is leading to a search for alternative pharmacological strategies. Adenosine is a major modulator of neuronal activity and neurotransmitter release in the central nervous system, with A1 receptors inhibiting transmitter release and A2 receptors generally enhancing release of several transmitter systems relevant to the control of movement. The A2a subtype of receptor is especially concentrated in the neostriatum and is co-localised with D2 receptors for dopamine, the affinity of which are reduced by activation of the A2a population. Antagonists of adenosine, such as theophylline, have been reported to improve the tremor in cases of Parkinson's disease and essential tremor, and the development of better and more selective A2a receptor antagonists may prove of value in these disabling disorders.