Resiniferatoxin

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Resiniferatoxin
Identifiers
CAS number 57444-62-9 N
PubChem 104826
ChemSpider 21106474 YesY
MeSH resiniferatoxin
ChEMBL CHEMBL448382 N
Jmol-3D images {{#if:Oc1ccc(cc1OC)CC(=O)OCC=4C[C@]7(O)C(=O)C(\C)=C/C7[C@]52O[C@@]3(O[C@](C[C@H]2C)(C(C)=C)C(O3)C5C=4)Cc6ccccc6|Image 1
Properties
Molecular formula C37H40O9
Molar mass 628.71 g/mol
Density 1.35 ± 0.1 g/cm³
Solubility in water insoluble
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references
Resiniferatoxin
Heat Above Peak (SR: 16,000,000,000)

Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco, and in Euphorbia poissonii found in northern Nigeria.[1] It is an ultrapotent analog of capsaicin, the active ingredient in chili pepper.[2]

It activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain).[3][4] RTX causes an ion channel in the plasma membrane of sensory neurons — the transient receptor potential vanilloid 1 — to become permeable to cations, most particularly the calcium cation; this evokes a powerful irritant effect followed by desensitization and analgesia.[5][6]

Research has been conducted at the National Institutes of Health[7][8] and the University of Pennsylvania[9] to design a novel class of analgesics from the latex of Euphorbia resinifera.

Total synthesis

A total synthesis of (+)-resiniferatoxin was completed by the Wender group at Stanford University in 1997.[10] As of 2007, this represented the only complete total synthesis of any member of the daphnane family of molecules.[11]

Toxicity

Resiniferatoxin is toxic and can inflict chemical burns. Animal experiments indicate that in humans ingestion of 40g or more may be fatal or cause serious damage to health.[12] Using the Scoville Scale, resiniferatoxin is estimated to have a rating of 16 billion, one thousand times higher than the rating for pure capsaicin.

See also

References

  1. ↑ Euphorbia poissonii in BoDD – Botanical Dermatology Database
  2. ↑
    • Christopher S. J. Walpole, et al. (1996). "Similarities and Differences in the Structure-Activity Relationships of Capsaicin and Resiniferatoxin Analogues". J. Med. Chem. 39 (15): 2939–2952. doi:10.1021/jm960139d. PMID 8709128. 
  3. ↑ Szallasi A, Blumberg PM (1989). "Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper". Neuroscience 30 (2): 515–520. doi:10.1016/0306-4522(89)90269-8. PMID 2747924. 
  4. ↑ Szallasi A, Blumberg PM (1990). "Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor". Life Sci. 47 (16): 1399–1408. doi:10.1016/0024-3205(90)90518-V. 
  5. ↑ Szallasi A, Blumberg PM (1992). "Vanilloid receptor loss in rat sensory ganglia associated with long term desensitization to resiniferatoxin". Neurosci Lett. 140 (1): 51–54. doi:10.1016/0304-3940(92)90679-2. PMID 1407700. 
  6. ↑ Olah Z et al. (2001). "Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1". J. Biol. Chem. 276 (14): 11021–11030. doi:10.1074/jbc.M008392200. PMID 11124944. 
  7. ↑ Neubert JK et al. (2003). "Peripherally induced resiniferatoxin analgesia". Pain 109 (1–2): 219–28. doi:10.1016/S0304-3959(03)00009-5. PMID 12855332. 
  8. ↑ Karai L et al. (2004). "Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control". J Clin Invest. 113 (9): 1344–1352. doi:10.1172/JCI20449. PMC 398431. PMID 15124026. 
  9. ↑ Brown DC et al. (2005). "Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model". Anesthesiology 103 (5): 1052–1059. doi:10.1097/00000542-200511000-00020. PMID 16249680. 
  10. ↑ Wender, P.A.; Jesudason, Cynthia D.; Nakahira, Hiroyuki; Tamura, Norikazu; Tebbe, Anne Louise; Ueno, Yoshihide (1997). "The First Synthesis of a Daphnane Diterpene: The Enantiocontrolled Total Synthesis of (+)-Resiniferatoxin". J. Am. Chem. Soc. 119 (52): 12976–12977. doi:10.1021/ja972279y. 
  11. ↑ http://www.scripps.edu/chem/baran/images/grpmtgpdf/Seiple_Mar_07.pdf
  12. ↑ Material Safety Data Sheet for resiniferatoxin, 2009

External links

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