Ecopipam

Ecopipam
Clinical data
ATC code none
Identifiers
CAS Number 112108-01-7 YesY
PubChem (CID) 107930
IUPHAR/BPS 3304
ChemSpider 97053
UNII 0X748O646K YesY
Chemical and physical data
Formula C19H20ClNO
Molar mass 313.821 g/mol
3D model (Jmol) Interactive image
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Ecopipam (SCH-39166) is a synthetic benzazepine derivative drug that acts as a selective dopamine D1/D5 receptor antagonist, with little affinity for either dopamine D2-like or 5-HT2 receptors.[1]

Clinical trials

Based on its profile in animal models, ecopipam was first studied as a treatment for schizophrenia but showed no activity.[2][3] Side effects including sedation, restlessness, emesis 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.[4] However, the effect did not persist following repeated administration.[5]

Researchers have postulated that dopamine via D1 receptors in the mesolimbic system is involved with rewarded behaviors and pleasure.[6] One such behavior is eating, and ecopipam has been shown in a large clinical study to be an effective treatment for obesity.[7] 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.

Recent (2014) open label studies have shown ecopipam to reduce gambling behaviors in subjects with pathological gambling[8] and to decrease the motor and vocal tics in adults with Tourette’s Syndrome.[9] Ecopipam is currently in clinical trials conducted by the biotechnology company Psyadon Pharmaceuticals for the treatment of Tourette syndrome in children ages 7–17.[10]

Chemical synthesis

Ecopipam can be synthesized from a simple tetralin derivative:[11]

References

  1. Chipkin 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): 1093–102. PMID 2905002.
  2. 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 (Berl). 121 (3): 309–16. doi:10.1007/bf02246068. PMID 8584611.
  3. Den Boer JA, van Megen HJ, Fleischhacker WW, Louwerens JW, Slaap BR, Westenberg HG, Burrows GD, Srivastava ON (October 1995). "Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia". Psychopharmacology (Berl). 121 (3): 317–22. doi:10.1007/bf02246069. PMID 8584612.
  4. 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 (Berl). 155 (4): 330–7. doi:10.1007/s002130100725. PMID 11441422.
  5. 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 (Berl). 155 (4): 338–47. doi:10.1007/s002130100724. PMID 11441423.
  6. Baik JH (October 11, 2013). "Dopamine signaling in reward-related behaviors". Front Neural Circuits. 7: 152. doi:10.3389/fncir.2013.00152. PMC 3795306Freely accessible. PMID 24130517.
  7. Astrup A, Greenway FL, Ling W, Pedicone L, Lachowicz J, Strader CD, Kwan R; Ecopipam Obesity Study Group (2007). "Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects". Obesity. 15 (7): 1717–31. doi:10.1038/oby.2007.205. PMID 17636090.
  8. 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". Ann Clin Psychiatry. 26 (3): 179–86. PMID 25166480.
  9. 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". Clin Neuropharmacol. 37 (1): 26–30. doi:10.1097/WNF.0000000000000017. PMID 24434529.
  10. http://clinicaltrials.gov/ct2/show/study/NCT02102698
  11. Hou, D; Schumacher, D (2001). "The selection of a commercial route for the D1 antagonist Sch-39166.". Current opinion in drug discovery & development. 4 (6): 792–9. PMID 11899619.



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