Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease

To investigate striatal adenosine A2A receptor availability in patients with Parkinson disease (PD) with and without levodopa-induced dyskinesias (LIDs). While providing effective relief from the motor symptoms of PD, chronic levodopa use is associated with development of LIDs. A2A receptors are expressed on the bodies of indirect pathway medium spiny striatal neurons and on dopamine terminals and play a role in modulating dopamine transmission. A2A antagonists have antiparkinsonian activity by boosting levodopa efficacy. We aimed to study A2A receptor availability in patients with PD with and without LIDs using PET and [¹¹C]SCH442416, an A2A antagonist.

Six patients with PD with and 6 without LIDs were studied withdrawn 12 hours from medication. Their PET findings were compared with 6 age-matched healthy controls. Using spectral analysis, [¹¹C]SCH442416 regional volumes of distribution (V(T)) were computed for the caudate, putamen, and thalamus and binding potentials (BP(ND)) reflecting the ratio of specific:nonspecific uptake were compared between groups.

A2A binding in the caudate and putamen of subjects with PD with LIDs was far higher (p = 0.026 and p = 0.036, respectively) than that of subjects with PD without LIDs, which lay within the control range. Thalamic A2A availability was similar for all 3 groups.

Patients with PD with LIDs show increased A2A receptor availability in the striatum. This finding is compatible with altered adenosine transmission playing a role in LIDs and provides a rationale for a trial of A2A receptor agents in the treatment of these motor complications.