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Other names | EBS-101; PSYRX-101; SCH-39166 |
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Chemical and physical data | |
Formula | C19H20ClNO |
Molar mass | 313.83 g·mol−1 |
3D model ( JSmol) | |
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Ecopipam (development codes SCH-39166, EBS-101, and PSYRX-101) is a dopamine antagonist which is under development for the treatment of Lesch-Nyhan syndrome, Tourette's syndrome, speech disorders, and restless legs syndrome. [1] It is taken by mouth. [2]
Ecopipam acts as a selective dopamine D1 and D5 receptor antagonist. [1] It is orally active, has an elimination half-life of 10 hours, crosses the blood–brain barrier, and substantially occupies brain dopamine receptors. [2] [3] Side effects of ecopipam may include depression, anxiety, fatigue, sedation, somnolence, insomnia, headaches, muscle twitching, and suicidal ideation, among others. [4] [5] [2] It appears to lack the typical extrapyramidal effects like tardive dyskinesia that occur with D2 receptor antagonists. [2]
Ecopipam is an experimental drug and has not been approved for medical use. [1] 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. [1] The drug was also under development for the treatment of cocaine-related disorders, obesity, and schizophrenia, but development for these indications was discontinued. [1]
Ecopipam is a selective dopamine D1 and D5 receptor antagonist. [6] It shows little affinity for either dopamine D2-like or 5-HT2 receptors. [6]
Based on its profile in animal models, ecopipam was first studied as a treatment for schizophrenia but showed no efficacy. [7] [8] 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. [9] However, the effect did not persist following repeated administration. [10]
Researchers have postulated that dopamine via D1 receptors in the mesolimbic system is involved with rewarded behaviors and pleasure. [11] One such behavior is eating, and ecopipam has been shown in a large clinical study to be an effective treatment for obesity. [12] 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. [13]
As of 2021, Emalex Biosciences is investigating its potential use for central nervous system disorders. [14] Open-label studies have found ecopipam to reduce gambling behaviors in subjects with pathological gambling [15] and to decrease the motor and vocal tics in adults with Tourette syndrome. [16] A subsequent double-blind placebo-controlled study in pediatric subjects confirmed ecopipam's ability to ameliorate the motor and vocal symptoms seen in patients with Tourette's syndrome. [17] Ecopipam is currently in a phase 2/ 3 clinical trial for the treatment of Tourette's syndrome in children ages 7 to 17. [18]
Ecopipam is additionally under development for the treatment of Lesch–Nyhan syndrome (phase 3) and restless legs syndrome (phase 1/2). [1]
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). [19] There are currently no U.S. Food and Drug Administration approved medications for the treatment of stuttering. [19]
Chemically, ecopipam is a synthetic benzazepine derivative. It can be synthesized from a simple tetralin derivative: [20]
Recently a study reported findings from human phase 2 and phase 3 clinical trials examining the potential of the D1/D5 receptor antagonist, ecopipam, to enhance and maintain weight loss in obese patients [61]. While these studies showed promising weight loss in both phase 2 and phase 3, there were unexpected treatment related neuropsychiatric adverse events (ecopipam 31% vs. placebo 15%) in the phase 3 clinical trials (that were not observed in the phase 2 studies) and as a consequence phase 3 studies were discontinued. The neuropsychiatric adverse events included depression (ecopipam 16% vs. placebo 6%), anxiety (ecopipam 15% vs. placebo 6%), suicidal ideation (ecopipam 2% vs. placebo 1%), insomnia (ecopipam 17% vs. placebo 7%), fatigue (ecopipam 15% vs. placebo 6%), and somnolence (ecopipam 15% vs. placebo 4%). Psychiatric adverse events also accounted for more than half of the discontinuations because of treatment related adverse effects in the ecopipam group.
Clinical data | |
---|---|
Other names | EBS-101; PSYRX-101; SCH-39166 |
ATC code |
|
Legal status | |
Legal status |
|
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
ChemSpider | |
UNII | |
CompTox Dashboard ( EPA) | |
Chemical and physical data | |
Formula | C19H20ClNO |
Molar mass | 313.83 g·mol−1 |
3D model ( JSmol) | |
| |
| |
(verify) |
Ecopipam (development codes SCH-39166, EBS-101, and PSYRX-101) is a dopamine antagonist which is under development for the treatment of Lesch-Nyhan syndrome, Tourette's syndrome, speech disorders, and restless legs syndrome. [1] It is taken by mouth. [2]
Ecopipam acts as a selective dopamine D1 and D5 receptor antagonist. [1] It is orally active, has an elimination half-life of 10 hours, crosses the blood–brain barrier, and substantially occupies brain dopamine receptors. [2] [3] Side effects of ecopipam may include depression, anxiety, fatigue, sedation, somnolence, insomnia, headaches, muscle twitching, and suicidal ideation, among others. [4] [5] [2] It appears to lack the typical extrapyramidal effects like tardive dyskinesia that occur with D2 receptor antagonists. [2]
Ecopipam is an experimental drug and has not been approved for medical use. [1] 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. [1] The drug was also under development for the treatment of cocaine-related disorders, obesity, and schizophrenia, but development for these indications was discontinued. [1]
Ecopipam is a selective dopamine D1 and D5 receptor antagonist. [6] It shows little affinity for either dopamine D2-like or 5-HT2 receptors. [6]
Based on its profile in animal models, ecopipam was first studied as a treatment for schizophrenia but showed no efficacy. [7] [8] 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. [9] However, the effect did not persist following repeated administration. [10]
Researchers have postulated that dopamine via D1 receptors in the mesolimbic system is involved with rewarded behaviors and pleasure. [11] One such behavior is eating, and ecopipam has been shown in a large clinical study to be an effective treatment for obesity. [12] 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. [13]
As of 2021, Emalex Biosciences is investigating its potential use for central nervous system disorders. [14] Open-label studies have found ecopipam to reduce gambling behaviors in subjects with pathological gambling [15] and to decrease the motor and vocal tics in adults with Tourette syndrome. [16] A subsequent double-blind placebo-controlled study in pediatric subjects confirmed ecopipam's ability to ameliorate the motor and vocal symptoms seen in patients with Tourette's syndrome. [17] Ecopipam is currently in a phase 2/ 3 clinical trial for the treatment of Tourette's syndrome in children ages 7 to 17. [18]
Ecopipam is additionally under development for the treatment of Lesch–Nyhan syndrome (phase 3) and restless legs syndrome (phase 1/2). [1]
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). [19] There are currently no U.S. Food and Drug Administration approved medications for the treatment of stuttering. [19]
Chemically, ecopipam is a synthetic benzazepine derivative. It can be synthesized from a simple tetralin derivative: [20]
Recently a study reported findings from human phase 2 and phase 3 clinical trials examining the potential of the D1/D5 receptor antagonist, ecopipam, to enhance and maintain weight loss in obese patients [61]. While these studies showed promising weight loss in both phase 2 and phase 3, there were unexpected treatment related neuropsychiatric adverse events (ecopipam 31% vs. placebo 15%) in the phase 3 clinical trials (that were not observed in the phase 2 studies) and as a consequence phase 3 studies were discontinued. The neuropsychiatric adverse events included depression (ecopipam 16% vs. placebo 6%), anxiety (ecopipam 15% vs. placebo 6%), suicidal ideation (ecopipam 2% vs. placebo 1%), insomnia (ecopipam 17% vs. placebo 7%), fatigue (ecopipam 15% vs. placebo 6%), and somnolence (ecopipam 15% vs. placebo 4%). Psychiatric adverse events also accounted for more than half of the discontinuations because of treatment related adverse effects in the ecopipam group.