Enadoline

Enadoline
Clinical data
Other namesCI-977; CI977
Drug classκ-Opioid receptor agonist; Hallucinogen
ATC code
  • None
Identifiers
  • 2-(1-Benzofuran-4-yl)-N-methyl-N-[(5R,7S,8S)-7-pyrrolidin-1-yl-1-oxaspiro[4.5]decan-8-yl]acetamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H32N2O3
Molar mass396.531 g·mol−1
3D model (JSmol)
  • O=C(Cc1cccc2occc12)N(C)C1CCC2(CCCO2)CC1N1CCCC1
  • InChI=1S/C24H32N2O3/c1-25(23(27)16-18-6-4-7-22-19(18)9-15-28-22)20-8-11-24(10-5-14-29-24)17-21(20)26-12-2-3-13-26/h4,6-7,9,15,20-21H,2-3,5,8,10-14,16-17H2,1H3/t20-,21-,24-/m0/s1 checkY
  • Key:JMBYBVLCYODBJQ-HFMPRLQTSA-N checkY
  (verify)

Enadoline (developmental code name CI-977) is a drug which acts as a highly selective κ-opioid agonist.

In human studies, it produced visual distortions and feelings of dissociation, reminiscent of the effects of salvinorin A.

It was studied as a potential analgesic, but abandoned because of the dose-limiting effects of dysphoria, which could be expected from a κ-opioid agonist. There was mention of its potential in treating comatose head injury or stroke victims, where that type of side effect would be immaterial. It has been found to reduce the euphoric effects of cocaine but did not alter cocaine self-administration in humans.

When enadoline was first reported in 1990, it was "the most potent κ-selective analgesic ever reported ... 25 times more potent than morphine and 17 times more potent than U-62066".

See also

References

  1. ↑ Walsh SL, Strain EC, Abreu ME, Bigelow GE (September 2001). "Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans". Psychopharmacology. 157 (2): 151–162. doi:10.1007/s002130100788. PMID 11594439. S2CID 10507758.
  2. ↑ Barber A, Gottschlich R (October 1997). "Novel developments with selective, non-peptidic kappa-opioid receptor agonists". Expert Opinion on Investigational Drugs. 6 (10): 1351–1368. doi:10.1517/13543784.6.10.1351. PMID 15989506.
  3. ↑ Gefke M, Wagner CB, McIntyre RS, Vinberg M (January 2026). "The Potential Clinical Use of Opioid-Receptor-Modulating Drugs in Bipolar Disorder". CNS Drugs. 40 (1): 59–70. doi:10.1007/s40263-025-01247-8. PMID 41222827.
  4. ↑ Walsh SL, Geter-Douglas B, Strain EC, Bigelow GE (October 2001). "Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans". J Pharmacol Exp Ther. 299 (1): 147–158. PMID 11561074.
  5. ↑ Halfpenny PR, Horwell DC, Hughes J, Hunter JC, Rees DC (January 1990). "Highly selective kappa-opioid analgesics. 3. Synthesis and structure-activity relationships of novel N-[2-(1-pyrrolidinyl)-4- or -5-substituted-cyclohexyl]arylacetamide derivatives". Journal of Medicinal Chemistry. 33 (1): 286–291. doi:10.1021/jm00163a047. PMID 2153208.