Resiniferatoxin
| Resiniferatoxin | |
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| Identifiers | |
| CAS number | 57444-62-9  |
| PubChem | 104826 |
| ChemSpider | 21106474  |
| MeSH | resiniferatoxin |
| ChEMBL | CHEMBL448382 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C37H40O9 |
| Molar mass | 628.71 g/mol |
| Density | 1.35 ± 0.1 g/cm³ |
 (verify) (what is:  / ?)Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
Resiniferatoxin (RTX) is a naturally occurring, ultrapotent capsaicin analog[1] that activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain).[2][3] 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.[4][5]
Research is being conducted at the National Institutes of Health[6][7] and the University of Pennsylvania[8] to design a novel class of analgesics from the latex of resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco that contains high concentrations of RTX.
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[edit] Total synthesis
A total synthesis of (+)-resiniferatoxin was completed by the Wender group at Stanford University in 1997.[9] As of 2007[update] this represented the only complete total synthesis of any member of the daphnane family of molecules.[10]
[edit] Toxicity
Resiniferatoxin is toxic and can produce chemical burns. Animal experiments indicate that ingestion of less than 40 g may be fatal or cause serious damage to health.[11]
[edit] See also
- Capsaicin
- Discovery and development of TRPV1 antagonists
- Iodoresiniferatoxin
- Transient receptor potential
- Tinyatoxin
[edit] References
- ^ *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.
- ^ 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): 515–20. doi:10.1016/0306-4522(89)90269-8. PMID 2747924.
- ^ Szallasi A, Blumberg PM (1990). "Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor". Life Sci. 47 (16): 1399–408. doi:10.1016/0024-3205(90)90518-V.
- ^ Szallasi A, Blumberg PM (1992). "Vanilloid receptor loss in rat sensory ganglia associated with long term desensitization to resiniferatoxin". Neurosci Lett. 140 (1): 51–4. doi:10.1016/0304-3940(92)90679-2. PMID 1407700.
- ^ Olah Z et al. (2001). "Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1". J. Biol. Chem. 276 (14): 11021–30. doi:10.1074/jbc.M008392200. PMID 11124944.
- ^ Neubert JK et al. (2003). "Peripherally induced resiniferatoxin analgesia". Pain 104 (1–2): 219–28. doi:10.1016/S0304-3959(03)00009-5. PMID 12855332.
- ^ Karai L et al. (2004). "Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control". J Clin Invest. 113 (9): 1344–52. doi:10.1172/JCI20449. PMC 398431. PMID 15124026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=398431.
- ^ Brown DC et al. (2005). "Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model". Anesthesiology 103 (5): 1052–9. doi:10.1097/00000542-200511000-00020. PMID 16249680.
- ^ 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.
- ^ http://www.scripps.edu/chem/baran/images/grpmtgpdf/Seiple_Mar_07.pdf
- ^ Material Safety Data Sheet for resiniferatoxin, 2009
