Epiboxidine

Epiboxidine is a chemical compound which acts as a partial agonist at neural nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. It was developed as a less toxic analogue of the potent frog-derived alkaloid epibatidine, which is around 200 times stronger than morphine as an analgesic but produces extremely dangerous toxic nicotinic side effects.

Epiboxidine
Legal status
Legal status
  • Investigational
Identifiers
IUPAC name
  • (1R,4S,6S)-6-(3-Methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H14N2O
Molar mass178.235 g·mol−1
3D model (JSmol)
SMILES
  • CC1=NOC(=C1)[C@H]2C[C@@H]3CC[C@H]2N3
InChI
  • InChI=1S/C10H14N2O/c1-6-4-10(13-12-6)8-5-7-2-3-9(8)11-7/h4,7-9,11H,2-3,5H2,1H3/t7-,8-,9+/m0/s1
  • Key:GEEFPQBPVBFCSD-XHNCKOQMSA-N

Epiboxidine is around one-tenth as potent as epibatidine as an α4β2 agonist, but has around the same potency as an α3β4 agonist. It has only one-tenth of the analgesic power of epibatidine, but is also much less toxic.[1][2][3]

Uses

Despite its decreased potency and toxicity compared to epibatidine, epiboxidine itself is still too toxic to be developed as a drug for use in humans. It is used in scientific research[4] and as a parent compound to derive newer analogues which may be safer and have greater potential for clinical development.[5][6][7]

See also

References
  1. Rizzi L, Dallanoce C, Matera C, Magrone P, Pucci L, Gotti C, et al. (August 2008). "Epiboxidine and novel-related analogues: a convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes" (PDF). Bioorganic & Medicinal Chemistry Letters. 18 (16): 4651–4. doi:10.1016/j.bmcl.2008.07.016. hdl:2434/59291. PMID 18644719.
  2. Dallanoce C, Matera C, De Amici M, Rizzi L, Pucci L, Gotti C, et al. (July 2012). "The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors". Chirality. 24 (7): 543–51. doi:10.1002/chir.22052. PMID 22566097.
  3. Badio B, Garraffo HM, Plummer CV, Padgett WL, Daly JW (February 1997). "Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine". European Journal of Pharmacology. 321 (2): 189–94. doi:10.1016/S0014-2999(96)00939-9. PMID 9063687.
  4. Yan X, Zhao B, Butt CM, Debski EA (December 2006). "Nicotine exposure refines visual map topography through an NMDA receptor-mediated pathway". The European Journal of Neuroscience. 24 (11): 3026–42. doi:10.1111/j.1460-9568.2006.05204.x. PMID 17156364. S2CID 25993659.
  5. Fitch RW, Pei XF, Kaneko Y, Gupta T, Shi D, Federova I, Daly JW (January 2004). "Homoepiboxidines: further potent agonists for nicotinic receptors". Bioorganic & Medicinal Chemistry. 12 (1): 179–90. doi:10.1016/j.bmc.2003.10.015. PMID 14697783.
  6. Cheng J, Izenwasser S, Zhang C, Zhang S, Wade D, Trudell ML (April 2004). "Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes". Bioorganic & Medicinal Chemistry Letters. 14 (7): 1775–8. doi:10.1016/j.bmcl.2004.01.025. PMID 15026069.
  7. Armstrong A, Bhonoah Y, Shanahan SE (October 2007). "Aza-Prins-pinacol approach to 7-azabicyclo[2.2.1]heptanes: syntheses of (+/-)-epibatidine and (+/-)-epiboxidine". The Journal of Organic Chemistry. 72 (21): 8019–24. doi:10.1021/jo701536a. PMID 17867705.
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