Description: GSK598809 is a novel, potent and selective dopamine D3 Receptor (DRD3) antagonist with a pKi of 8.9. GSK598809 is currently in Phase I trials. GSK-598809 may decrease the rewarding effects of contextual cues associated with drug intake preclinically, which may reduce drug craving in humans. GSK598809 has been proposed as a medication to treat cocaine and other substance use disorders. The US Food and Drug Administration has established guidelines recommending safety studies to investigate potential undesirable pharmacodynamic effects of a substance in relation to exposure in the therapeutic range and above. GSK598809 increased the hemodynamic effect of cocaine in this model. Thus, the increase in blood pressure after intravenous cocaine was greater in animals that had been pretreated with GSK598809 compared with vehicle. This finding suggests that GSK598809 in particular, and perhaps dopamine D3 receptor antagonists as a class, may produce unacceptable cardiovascular risks as medications to treat cocaine use disorder.