Targeting Dopamine Pathways for the Treatment of Tourette Syndrome

Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by motor and vocal tics that can reduce quality of life. The pathophysiology of TS is not yet fully understood, but existing evidence implicates excess dopaminergic activity in the basal ganglia. Most pharmacotherapies for TS decrease dopamine signaling to some degree, although the efficacy and safety profiles of these medications differ. For example, antipsychotics that target the dopamine D ₂ receptor (D2R) are considered highly efficacious but are associated with adverse effects that limit their therapeutic potential. Ecopipam is a selective dopamine D ₁ receptor (D1R) antagonist under investigation for treatment of TS. Selective antagonist activity at D1Rs, which differ in distribution and function from D2Rs, may reduce tic severity while avoiding some of the safety risks of D2R-targeting antipsychotics. This review discusses the burden, pathophysiology, and pharmacologic treatment of TS with a focus on ecopipam as a potential therapy.