Ecopipam

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Ecopipam
Ecopipam structure.png
Systematic (IUPAC) name
(–)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naptho-(2,1-b)azepine
Clinical data
Legal status
?
Identifiers
CAS number 112108-01-7 YesY
ATC code None
PubChem CID 107930
UNII 0X748O646K YesY
Chemical data
Formula C19H20ClNO 
Mol. mass 313.821 g/mol
 YesY (what is this?)  (verify)

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]

Chemical synthesis[edit]

Ecopipam can be synthesized from a simple tetralin derivative:[2]

Ecopipam scheme.png

Clinical trials[edit]

Based on its profile in animal models, Ecopipam was first studied as a treatment for schizophrenia but showed no activity.[3][4] 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.[5] However, the effect did not persist following repeated administration.[6]

Researchers have postulated that dopamine via D1 receptors in the mesolimbic system is involved with rewarded behaviors and pleasure.[7] One such behavior is eating, and Ecopipam has been shown in a large clinical study to be an effective treatment for obesity.[8] 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[9] and to decrease the motor and vocal tics in adults with Tourette’s Syndrome.[10] Ecopipam is currently in clinical trials conducted by the biotechnology company Psyadon Pharmaceuticals for the treatment of Tourette’s Syndrome in children ages 7–17.[11]

References[edit]

  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. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Baik JH (October 11, 2013). "Dopamine signaling in reward-related behaviors". Front Neural Circuits 7: 152. doi:10.3389/fncir.2013.00152. PMC 3795306. PMID 24130517. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ http://clinicaltrials.gov/ct2/show/study/NCT02102698