Ecopipam

Ecopipam (SCH-39166) is a synthetic benzazepine derivative drug that acts as a selective dopamine D₁/D₅ receptor antagonist, with little affinity for either dopamine D₂-like or 5-HT₂ receptors.

Chemical synthesis

Ecopipam can be synthesized from a simple tetralin derivative:

Clinical trials

Based on its profile in animal models, ecopipam was first studied as a treatment for schizophrenia but showed no activity. Side effects including sedation, restlessness, emesis and anxiety were generally rated mild. There were no reports of Parkinsonian-like extrapyramidal symptoms typically seen with D₂ antagonists.

Human clinical studies also showed that ecopipam was an effective antagonist of the acute euphoric effects of cocaine. However, the effect did not persist following repeated administration.

Researchers have postulated that dopamine via D₁ receptors in the mesolimbic system is involved with rewarded behaviors and pleasure. One such behavior is eating, and ecopipam has been shown in a large clinical study to be an effective treatment for obesity. However, reports of mild-to-moderate, reversible anxiety and depression made it unsuitable for commercialization as an anti-obesity drug, and its development was stopped.