Epibatidine

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ImageFile=Epibatidine structure.pngImageSize=
IUPACName=(4"S",6"R")-6-(6-chloro-3-pyridyl)-7-azabicyclo [2.2.1] heptane
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Section1= Chembox Identifiers
CASNo=140111-52-0
PubChem=105084
SMILES=C1CC2C(CC1N2)C3=CN=C(C=C3)Cl
MeSHName=Epibatidine
Section2= Chembox Properties
Formula=C₁₁H₁₃ClN₂
MolarMass=208.687
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MeltingPt=59-66 °C
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Section3= Chembox Hazards
MainHazards=Highly toxic
FlashPt=
Autoignition=

Epibatidine is an alkaloid that originally is found in the skin of a neotropical poisonous frog, "Epipedobates tricolor", found in modern Ecuador. It was initially isolated by John Daly at the National Institutes of Health, and was found to be a powerful analgesic, about 200 times more potent than morphine. [* [http://www.phc.vcu.edu/Feature/oldfeature/epi/ Epibatidine] - A review by Matthew J. Dowd] Because the natural source of epibatidine can only supply a small quantity, several laboratory syntheses have been developed. [Olivo, Horacio F.; Hemenway, Michael S. Recent syntheses of epibatidine. A review. "Organic Preparations and Procedures International" (2002), 34(1), 1-26.]

Interestingly, the compound is not an opioid; instead, it is similar to nicotine and appears to act by binding and activating nicotinic acetylcholine receptors. While epibatidine may be too toxic to use in clinical practice, the compound represents a new lead in the drug design of new analgesics. [Carroll, F. Ivy. Epibatidine structure-activity relationships. "Bioorganic & Medicinal Chemistry Letters" (2004), 14(8), 1889-1896.]

Of the tested epibatidine derivatives, Abbot Labs' ABT-594 (Tebanicline) is the most promising reported to date. ABT-594 was discovered to be 50 times more potent than morphine, yet on animal tests, no paralysis or depression of muscle action was observed. It completed Phase II clinical trials in Europe, [ [http://www.chemsoc.org/ExemplarChem/entries/2004/icl_Pan/page5.html The New Morphine] ] but while it showed clinical efficacy for treating neuropathic pain in humans it was dropped from further development due to unacceptable incidence of gastrointestinal side effects. [Meyer MD. Neuronal Nicotinic Acetylcholine Receptors as a Target for the Treatment of Neuropathic Pain. "Drug Development Research". 2006; 67: 355-359.] Further research in this area is ongoing. [Bunnelle WH, Daanen JF, Ryther KB, Schrimpf MR, Dart MJ, Gelain A, Meyer MD, Frost JM, Anderson DJ, Buckley M, Curzon P, Cao YJ, Puttfarcken P, Searle X, Ji J, Putman CB, Surowy C, Toma L, Barlocco D. Structure-activity studies and analgesic efficacy of N-(3-pyridinyl)-bridged bicyclic diamines, exceptionally potent agonists at nicotinic acetylcholine receptors. "Journal of Medicinal Chemistry". 2007 Jul 26;50(15):3627-44. PMID 17585748]

References

External links

* [http://www.chemsoc.org/ExemplarChem/entries/2004/icl_Pan/index.html# Epibatidine at chemsoc.org]