Dopamine replacement
therapy using the
dopamine precursor,
l-3,4-dihydroxyphenylalanine (
l-DOPA), with a peripheral
dopa decarboxylase inhibitor is the most effective treatment currently available for the symptoms of
Parkinson's disease (PD). However, the long-term use of dopaminergic
therapies for PD is often limited by the development of motor response complications, such as
dyskinesia.
Adenosine A2A receptors are a promising nondopaminergic target for the treatment of PD. The treatment of motor response complications involves combinations of regular and controlled release
L-DOPA, perhaps with the addition of a COMT inhibitor or the use of a longer-acting
dopamine agonist. However, when
dyskinesia is already established, the increase in dopaminergic load produced by the addition of a
dopamine agonist can result in an increase in the severity and duration of
dyskinesia. Currently, there are no well-tolerated antidyskinesia agents available.
Amantadine, which may exert its effects through the inhibition of
N-methyl-D-aspartate (
NMDA) receptors, shows some effects on established
dyskinesia.
Dyskinesia has a negative impact on the quality of life of patients, sometimes being more disabling than PD itself. Although some patients prefer experiencing
dyskinesia than being in the OFF state and unable to move, alternative, more effective
therapies are still required for severe disabling
dyskinesia to afford patients an improved quality of life while in the ON state. The mechanisms causing and maintaining the
dyskinesia have not been clarified. The application of a nondopaminergic approach to modify the basal ganglial activity would be helpful to better understand and treat
dyskinesia. The use of an
adenosine A2A receptor may provide one such approach. In this literature review, we will summarize the current knowledge from both clinical and nonclinical studies on the effects of
adenosine A2A receptor blockade on
dyskinesia.