SYN115

SYN115 is a novel, selective adenosine A(2A) receptor antagonist. The selective adenosine A(2A) receptor antagonists have been proposed as therapeutic tools for dopaminergically-relevant diseases. Adenosine A(2a) receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally focused attention, consistent with decreased self-reported sleepiness on SYN115. In cocaine-dependent subjects, SYN115 may produce stimulant-like effects through a unique mechanism of action. We conclude that SYN115 enters the brain and exerts dose-dependent regional effects, the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies.