Ecopipam (development codes SCH-39166, EBS-101, and PSYRX-101) is a
dopamine antagonist
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have ...
which is under development for the treatment of
Lesch-Nyhan syndrome,
Tourette's syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
,
speech disorder
Speech disorders or speech impairments are a type of communication disorder in which normal speech is disrupted. This can mean stuttering, lisps, etc. Someone who is unable to speak due to a speech disorder is considered mute. Speech skills ...
s, and
restless legs syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
.
It is taken
by mouth
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
.
Ecopipam acts as a
selective dopamine D1 and
D5 receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
antagonist.
It is
orally active, has an
elimination half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of 10hours, crosses the
blood–brain barrier, and substantially occupies brain dopamine receptors.
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s of ecopipam may include
depression,
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
fatigue,
sedation,
somnolence
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
,
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
,
headaches,
muscle twitching
A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serio ...
, and
suicidal ideation, among others.
It appears to lack the typical
extrapyramidal effects like
tardive dyskinesia
Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...
that occur with
D2 receptor antagonists.
Ecopipam is an
experimental drug
An experimental drug is a medicinal product (a drug or vaccine) that has not yet received approval from governmental regulatory authorities for routine use in human or veterinary medicine. A medicinal product may be approved for use in one diseas ...
and has not been approved for medical use.
As of April 2022, it is in
phase 3 trials for Lesch-Nyhan syndrome,
phase 2 trials for Tourette's syndrome and speech disorders, and phase 2/
phase 1 trials for restless legs syndrome.
The drug was also under development for the treatment of
cocaine-related disorders,
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, and
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...
, but development for these indications was discontinued.
Pharmacology
Pharmacodynamics
Ecopipam is a
selective dopamine D1 and
D5 receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
antagonist.
It shows little
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Par ...
for either dopamine
D2-like or
5-HT2 receptors.
Clinical trials
Based on its profile in
animal model
An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...
s, ecopipam was first studied as a treatment for
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...
but showed no efficacy.
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s including
sedation,
restlessness,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, and
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
were generally rated mild. There were no reports of
Parkinsonian
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy b ...
-like
extrapyramidal symptoms
Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...
typically seen with
D2 antagonists.
Human clinical studies also showed that ecopipam was an effective antagonist of the acute
euphoric
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
effects of
cocaine
Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...
.
However, the effect did not persist following repeated administration.
Researchers have postulated that dopamine via D
1 receptors in the
mesolimbic system is involved with
rewarded behaviors and pleasure.
One such behavior is
eating
Eating (also known as consuming) is the ingestion of food, typically to provide a heterotrophic organism with energy and to allow for growth. Animals and other heterotrophs must eat in order to survive — carnivores eat other animals, he ...
, and ecopipam has been shown in a large clinical study to be an effective treatment for
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
.
However, reports of mild-to-moderate, reversible anxiety and
depression made it unsuitable for commercialization as an
anti-obesity drug
Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control weight. These medications alter one of the fundamental processes of the human body, weight regulation, by altering either appetite, or absorp ...
, and its development was stopped for that indication.
As of 2021, Emalex Biosciences is investigating its potential use for
central nervous system disorders.
Open-label studies have found ecopipam to reduce
gambling
Gambling (also known as betting or gaming) is the wagering of something of value ("the stakes") on a random event with the intent of winning something else of value, where instances of strategy are discounted. Gambling thus requires three el ...
behaviors in subjects with
pathological gambling and to decrease the
motor and vocal tics in adults with
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
.
A subsequent
double-blind
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...
placebo-controlled study
Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed ...
in pediatric subjects confirmed ecopipam's ability to ameliorate the motor and vocal symptoms seen in patients with Tourette's syndrome. Ecopipam is currently in a
phase 2/
3 clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
for the treatment of Tourette's syndrome in children ages 7 to 17.
Ecopipam is additionally under development for the treatment of
Lesch–Nyhan syndrome
Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the ''HPRT1'' gene located on the X chromosome. LNS ...
(phase 3) and
restless legs syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
(phase 1/2).
Ecopipam is an investigational first-in-class drug being evaluated for the treatment of childhood-onset fluency disorder (
stuttering) in adults. It is under development for the treatment of
stuttering (phase 2).
There are currently no U.S. Food and Drug Administration approved medications for the treatment of stuttering.
Chemistry
Chemically, ecopipam is a
synthetic benzazepine
Benzazepines are heterocyclic chemical compounds consisting of a benzene ring fused to an azepine ring. Examples include:
File:Benazepril structure.svg, Benazepril
File:Fenoldopam.svg, Fenoldopam
File:GSK-189,254.svg, GSK-189,254
File:Ivabradine ...
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
. It can be
synthesized from a simple
tetralin
Tetralin (1,2,3,4-tetrahydronaphthalene) is a hydrocarbon having the chemical formula C10H12. It is a partially hydrogenated derivative of naphthalene. It is a colorless liquid that is used as a hydrogen-donor solvent.
Production
Tetralin is pro ...
derivative:
:
References
{{Xenobiotic-sensing receptor modulators
1-Phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
Chloroarenes
Dopamine antagonists
Phenols