1. A clinical trial of safety and tolerability for the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease
- Author
-
Hyder A. Jinnah, Tanya Khasnavis, Richard Chipkin, William L. Nyhan, Gail E. Reiner, and Barbara Sommerfeld
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Lesch-Nyhan Syndrome ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Population ,Ecopipam ,Bioinformatics ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Endocrinology ,Dopamine receptor D1 ,Genetics ,medicine ,Humans ,Psychiatry ,education ,Child ,Molecular Biology ,education.field_of_study ,business.industry ,Receptors, Dopamine D1 ,Dopamine antagonist ,Benzazepines ,Middle Aged ,Receptor antagonist ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,chemistry ,Tolerability ,Clinical Global Impression ,Dopamine Antagonists ,business ,Self-Injurious Behavior ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2016