JJC8-089

JJC8-089
Clinical data
Drug classDopamine reuptake inhibitor
Identifiers
  • 1-[4-[2-[bis(4-fluorophenyl)methylsulfanyl]ethyl]piperazin-1-yl]propan-2-ol
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC22H28F2N2OS
Molar mass406.54 g·mol−1
3D model (JSmol)
  • CC(CN1CCN(CC1)CCSC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F)O
  • InChI=1S/C22H28F2N2OS/c1-17(27)16-26-12-10-25(11-13-26)14-15-28-22(18-2-6-20(23)7-3-18)19-4-8-21(24)9-5-19/h2-9,17,22,27H,10-16H2,1H3
  • Key:MQDDJWTVOBHYHX-UHFFFAOYSA-N

JJC8-089 is a dopamine reuptake inhibitor (DRI) that was derived from modafinil and is related to JJC8-016, JJC8-088, and JJC8-091.[1][2] Its affinity (Ki) for the dopamine transporter (DAT) is 37.8 nM, for the norepinephrine transporter (NET) is 11,820 nM (313-fold lower than for the DAT), for the serotonin transporter (SERT) is 6,800 nM (180-fold lower than for the DAT), and for the sigma σ1 receptor is 2.24 nM (17-fold higher than for the DAT).[2][3] It also has significant affinity for several dopamine receptors.[3] JJC8-089 has substantially higher affinity for the DAT than modafinil.[1][2][3] The drug shows pro-motivational effects in animals.[4][5] It was first described in the scientific literature by 2016.[6][7]

See also

References

  1. ^ a b Aggarwal S, Mortensen OV (2023). "Discovery and Development of Monoamine Transporter Ligands". Drug Development in Psychiatry. Advances in Neurobiology. Vol. 30. pp. 101–129. doi:10.1007/978-3-031-21054-9_4. ISBN 978-3-031-21053-2. PMC 10074400. PMID 36928847. {{cite book}}: |journal= ignored (help)
  2. ^ a b c Newman AH, Ku T, Jordan CJ, Bonifazi A, Xi ZX (January 2021). "New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders". Annu Rev Pharmacol Toxicol. 61: 609–628. doi:10.1146/annurev-pharmtox-030220-124205. PMC 9341034. PMID 33411583.
  3. ^ a b c Giancola JB, Bonifazi A, Cao J, Ku T, Haraczy AJ, Lam J, Rais R, Coggiano MA, Tanda G, Newman AH (December 2020). "Structure-activity relationships for a series of (Bis(4-fluorophenyl)methyl)sulfinylethyl-aminopiperidines and -piperidine amines at the dopamine transporter: Bioisosteric replacement of the piperazine improves metabolic stability". Eur J Med Chem. 208: 112674. doi:10.1016/j.ejmech.2020.112674. PMC 7680422. PMID 32947229.
  4. ^ Salamone JD, Correa M (January 2024). "The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine". Annu Rev Psychol. 75: 1–32. doi:10.1146/annurev-psych-020223-012208. hdl:10234/207207. PMID 37788571.
  5. ^ Ecevitoglu A, Meka N, Rotolo RA, Edelstein GA, Srinath S, Beard KR, Carratala-Ros C, Presby RE, Cao J, Okorom A, Newman AH, Correa M, Salamone JD (July 2024). "Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors". Neuropsychopharmacology. 49 (8): 1309–1317. doi:10.1038/s41386-024-01826-1. PMC 11224370. PMID 38429498.
  6. ^ Cao J, Slack RD, Bakare OM, Burzynski C, Rais R, Slusher BS, Kopajtic T, Bonifazi A, Ellenberger MP, Yano H, He Y, Bi GH, Xi ZX, Loland CJ, Newman AH (December 2016). "Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors". J Med Chem. 59 (23): 10676–10691. doi:10.1021/acs.jmedchem.6b01373. PMC 5161041. PMID 27933960.
  7. ^ Tunstall BJ, Ho CP, Cao J, Vendruscolo JC, Schmeichel BE, Slack RD, Tanda G, Gadiano AJ, Rais R, Slusher BS, Koob GF, Newman AH, Vendruscolo LF (March 2018). "Atypical dopamine transporter inhibitors attenuate compulsive-like methamphetamine self-administration in rats". Neuropharmacology. 131: 96–103. doi:10.1016/j.neuropharm.2017.12.006. PMC 5820113. PMID 29217282.
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