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]
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]
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]
^ abcdKhasnavis T, Torres RJ, Sommerfeld B, Puig JG, Chipkin R, Jinnah HA (July 2016). "A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease". Molecular Genetics and Metabolism. 118 (3): 160–166. doi:10.1016/j.ymgme.2016.04.012. PMID27179999.
^Karlsson P, Sedvall G, Halldin C, Swahn CG, Farde L (October 1995). "Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man". Psychopharmacology. 121 (3): 300–308. doi:10.1007/BF02246067. PMID8584610. S2CID12659381.
^Nathan PJ, O'Neill BV, Napolitano A, Bullmore ET (October 2011). "Neuropsychiatric adverse effects of centrally acting antiobesity drugs". CNS Neuroscience & Therapeutics. 17 (5): 490–505. doi:10.1111/j.1755-5949.2010.00172.x. PMC6493804. PMID21951371. 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.
^Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE (2014). "A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome". Clinical Neuropharmacology. 37 (1): 26–30. doi:10.1097/WNF.0000000000000017. PMID24434529. S2CID24829565.
^ abChipkin RE, Iorio LC, Coffin VL, McQuade RD, Berger JG, Barnett A (December 1988). "Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity". The Journal of Pharmacology and Experimental Therapeutics. 247 (3): 1093–1102. PMID2905002.
^Karlsson P, Smith L, Farde L, Härnryd C, Sedvall G, Wiesel FA (October 1995). "Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients". Psychopharmacology. 121 (3): 309–316. doi:10.1007/bf02246068. PMID8584611. S2CID23909094.
^Den Boer JA, van Megen HJ, Fleischhacker WW, Louwerens JW, Slaap BR, Westenberg HG, et al. (October 1995). "Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia". Psychopharmacology. 121 (3): 317–322. doi:10.1007/bf02246069. PMID8584612. S2CID21837432.
^Haney M, Ward AS, Foltin RW, Fischman MW (June 2001). "Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self-administration by humans". Psychopharmacology. 155 (4): 330–337. doi:10.1007/s002130100725. PMID11441422. S2CID973041.
^Nann-Vernotica E, Donny EC, Bigelow GE, Walsh SL (June 2001). "Repeated administration of the D1/5 antagonist ecopipam fails to attenuate the subjective effects of cocaine". Psychopharmacology. 155 (4): 338–347. doi:10.1007/s002130100724. PMID11441423. S2CID854984.
^Grant JE, Odlaug BL, Black DW, Fong T, Davtian M, Chipkin R, Kim SW (August 2014). "A single-blind study of 'as-needed' ecopipam for gambling disorder". Annals of Clinical Psychiatry. 26 (3): 179–186. PMID25166480.
^Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE (January–February 2014). "A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome". Clinical Neuropharmacology. 37 (1): 26–30. doi:10.1097/WNF.0000000000000017. PMID24434529. S2CID24829565.
^Gilbert DL, Murphy TK, Jankovic J, Budman CL, Black KJ, Kurlan RM, et al. (August 2018). "Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study". Movement Disorders. 33 (8): 1272–1280. doi:10.1002/mds.27457. PMID30192018. S2CID52169188.
^Clinical trial number NCT04007991 for "Multicenter, Placebo-Controlled, Double-Blind, Randomized, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Ecopipam in Children and Adolescents With Tourette's Syndrome" at ClinicalTrials.gov
^Hou D, Schumacher D (November 2001). "The selection of a commercial route for the D1 antagonist Sch-39166". Current Opinion in Drug Discovery & Development. 4 (6): 792–799. PMID11899619.
