title: A clinical trial of safety and tolerability for the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease.
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.
authors.affiliation: Department of Neurology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Khasnavis
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Reiner
authors.affiliation: Department of Neurology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sommerfeld
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Nyhan
authors.affiliation: Psyadon Pharmaceuticals, 20451 Seneca Meadows Parkway, Germantown, MD 20876, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chipkin
authors.affiliation: 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.
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
mesh_terms: D000293:Adolescent; D000328:Adult; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D016728:Self-Injurious Behavior; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam
keywords: Dopamine antagonist; Dystonia; Impulsive behavior; Self-injurious behavior; Treatment trial