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

Tanya Khasnavis; Gail Reiner; Barbara Sommerfeld; William L Nyhan; Richard Chipkin; H A Jinnah

doi:10.1016/j.ymgme.2016.02.005

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

Mol Genet Metab. 2016 Apr;117(4):401-6. doi: 10.1016/j.ymgme.2016.02.005. Epub 2016 Feb 18.

Authors

Tanya Khasnavis¹, Gail Reiner², Barbara Sommerfeld¹, William L Nyhan², Richard Chipkin³, H A Jinnah⁴

Affiliations

¹ Department of Neurology, Emory University, Atlanta, GA 30322, USA.
² Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
³ Psyadon Pharmaceuticals, 20451 Seneca Meadows Parkway, Germantown, MD 20876, USA.
⁴ Department of Neurology, Emory University, Atlanta, GA 30322, USA; Department of Human Genetics, Emory University, Atlanta, GA 30322, USA; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address: hjinnah@emory.edu.

PMID: 26922636
DOI: 10.1016/j.ymgme.2016.02.005

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.

Keywords: Dopamine antagonist; Dystonia; Impulsive behavior; Self-injurious behavior; Treatment trial.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Benzazepines / administration & dosage
Benzazepines / adverse effects
Benzazepines / therapeutic use*
Child
Dopamine Antagonists / administration & dosage
Dopamine Antagonists / adverse effects
Dopamine Antagonists / therapeutic use*
Humans
Lesch-Nyhan Syndrome / diagnosis
Lesch-Nyhan Syndrome / drug therapy*
Lesch-Nyhan Syndrome / metabolism
Male
Middle Aged
Receptors, Dopamine D1 / antagonists & inhibitors*
Self-Injurious Behavior
Treatment Outcome
Young Adult

Substances

Benzazepines
Dopamine Antagonists
Receptors, Dopamine D1
ecopipam