A clinical trial of safety and tolerability for the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease

作者：Khasnavis Tanya; Reiner Gail; Sommerfeld Barbara; Nyhan William L; Chipkin Richard; Jinnah H A^*

来源：Molecular Genetics and Metabolism, 2016, 117(4): 401-406.

DOI：10.1016/j.ymgme.2016.02.005

• Self-injurious behavior
• Impulsive behavior
• Dystonia
• Treatment trial
• Dopamine antagonist

Lesch-Nyhan disease (LND) is an inherited metabolic disorder characterized by the overproduction of uric acid and distinct behavioral, cognitive, and motor abnormalities. The most challenging clinical problem is self injurious behavior (SIB), which includes self-biting, self-hitting, self-abrasion, and other features. Currently, these behaviors are managed by behavioral extinction, sedatives, physical restraints, and removal of teeth. More effective treatments are needed. Pre-clinical studies have led to the hypothesis that D1-dopamine receptor antagonists may provide useful treatments for SIB in LND. Ecopipam is one such selective D1-dopamine receptor antagonist This report summarizes results of a dose-escalation study of the safety and tolerability of ecopipam in 5 subjects with LND. The results suggest that ecopipam is well tolerated, with sedation being the most common dose-limiting event Several exploratory measures also suggest ecopipam might reduce SIB in this population. These results support the hypothesis that D1-dopamine receptor antagonists may be useful for suppressing SIB in LND, and encourage further studies of efficacy.

• 出版日期2016-4