Based on its profile in
animal models, ecopipam was first studied as a treatment for
schizophrenia but showed no efficacy.
Side effects including
sedation,
restlessness,
vomiting, and
anxiety were generally rated mild. There were no reports of
Parkinsonian-like
extrapyramidal symptoms typically seen with
D2 antagonists. Human clinical studies also showed that ecopipam was an effective antagonist of the acute
euphoric effects of
cocaine. However, the effect did not persist following repeated administration.
Open-label studies found ecopipam to reduce
gambling behaviors in subjects with
pathological gambling. Researchers have postulated that dopamine via D1 receptors in the
mesolimbic system are involved with
rewarded behaviors and pleasure. One such behavior is
eating, and ecopipam has been shown in a large clinical study to be an effective treatment for
obesity. However, reports of mild-to-moderate, reversible anxiety and
depression made it unsuitable for commercialization as an
anti-obesity drug, and its development was stopped for that indication. Ecopipam was under development for the treatment of
Lesch–Nyhan syndrome and
restless legs syndrome. There are currently no U.S.
Food and Drug Administration (FDA) approved medications for this disorder.
Open-label studies found ecopipam to decrease
tic severity in adults with
Tourette syndrome. A subsequent
double-blind placebo-controlled study confirmed ecopipam's ability to ameliorate
motor and vocal tics in pediatric participants with Tourette syndrome. A subsequent parallel-group, randomized,
placebo-controlled clinical trial in children ages 7 to 17 with Tourette syndrome found ecopipam superior to placebo in reducing tic severity; response, defined as a 25% or greater improvement on the standard tic severity scale (
YGTSS total tic score), occurred in 74% of participants taking ecopipam versus 43% of those on placebo (odds ratio 3.7, 95%
CI 1.8 to 7.4), for a
number needed to treat of 3.0. Overall ecopipam was well tolerated, without evidence of the motor or metabolic side effects common to
D2 receptor antagonists. Ecopipam is also being studied for the treatment of restless legs syndrome augmentation (phase 1/2). ==Chemistry==