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Cardiovascular and Subjective Effects of the Novel Adenosine A_2A ReceptorAntagonist SYN115 in Cocaine Dependent Individuals

Lane SD, Green CE, Steinberg JL, Ma L, Schmitz JM, Rathnayaka N, Bandak SD, Ferre S and Moeller FG

A_2A receptor antagonists have been proposed as therapeutic tools for dopaminergically-relevant diseases, including Parkinson's disease and substance dependence. The acute subjective and cardiovascular effects of a novel, selective adenosine A_2A receptor antagonist (SYN115) were examined. Across an 8-hour experimental testing day, 22 nontreatment seeking cocaine-dependent subjects received either placebo capsules (PO) at both the AM and PM dosing times (Plc/Plc, N = 9), or placebo in the AM and 100 mg SYN115 in the PM (Plc/SYN115, N =13). Cardiovascular measures (HR, BP) were obtained across the test day, and subjective effects (ARCI, VAS) were obtained once before and once after the AM and PM doses (four time points total). There were no between-group effects on cardiovascular function, however subjective effects consistent with stimulation were observed on the VAS scales in the SYN115 group. In cocaine-dependent subjects, SYN115 may produce stimulant-like effects through a unique mechanism of action. Due to known monoamine dysfunction related to chronic cocaine use, these effects may be specific to this population relative to healthy control or other patient populations.