Epiboxidine

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ImageFile=Epiboxidine.pngImageSize=240
IUPACName=(1"R",4"S",6"S")-6-(3-methyl-5-isoxazolyl)- 7-azabicyclo [2.2.1] heptane
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CASNo=188895-96-7
PubChem=5747670
SMILES=CC1=NOC(=C1) [C@H] 2C [C@@H] 3CC [C@H] 2N3
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C=10 | H=14 | N=2 | O=1
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Section3=Chembox Hazards
MainHazards=Toxic
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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 side effects.

Epiboxidine is around ten times less potent than 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. [Badio B, Garraffo HM, Plummer CV, Padgett WL, Daly JW. Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine. "European Journal of Pharmacology". 1997 Feb 26;321(2):189-94. PMID 9063687]

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 [Yan X, Zhao B, Butt CM, Debski EA. Nicotine exposure refines visual map topography through an NMDA receptor-mediated pathway. "European Journal of Neuroscience". 2006 Dec;24(11):3026-42. PMID 17156364] and as a parent compound to derive newer analogues which may be safer and have greater potential for clinical development. [Fitch RW, Pei XF, Kaneko Y, Gupta T, Shi D, Federova I, Daly JW. Homoepiboxidines: further potent agonists for nicotinic receptors. "Bioorganic and Medicinal Chemistry". 2004 Jan 2;12(1):179-90. PMID 14697783] [Cheng J, Izenwasser S, Zhang C, Zhang S, Wade D, Trudell ML. Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo [3.2.1] octanes. "Bioorganic and Medicinal Chemistry Letters". 2004 Apr 5;14(7):1775-8. PMID 15026069] [Armstrong A, Bhonoah Y, Shanahan SE. Aza-Prins-pinacol approach to 7-azabicyclo [2.2.1] heptanes: syntheses of (+/−)-epibatidine and (+/−)-epiboxidine. "Journal of Organic Chemistry". 2007 Oct 12;72(21):8019-24. PMID 17867705]

References