| Revision as of 10:04, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Saving copy of the {{chembox}} taken from revid 464330950 of page Cantharidin for the Chem/Drugbox validation project (updated: 'ChEMBL', 'KEGG', 'CASNo'). |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Use American English|date=September 2023}} |
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{{Use dmy dates|date=September 2023}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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| verifiedrevid = 457286325 |
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| verifiedrevid = 464365947 |
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| Name = Cantharidin |
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| ImageFile = Cantharidin structure.png |
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| Name = Cantharidin |
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| ImageFile = Cantharidin-2D.svg |
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| ImageSize = |
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| ImageSize = 150px |
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| IUPACName = 2,6-Dimethyl-4,10-dioxatricyclo-<br />decane-3,5-dione |
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| OtherNames = Cantharidin |
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| ImageFile2 = Cantharidin-3D.png |
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| ImageSize2 = 150px |
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| Section1 = {{Chembox Identifiers |
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| PIN = (3a''R'',4''S'',7''R'',7a''S'')-3a,7a-Dimethylhexahydro-4,7-epoxybenzofuran-1,3-dione |
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| CASNo_Ref = {{cascite|changed|??}} |
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| OtherNames = {{ubl | Cantharidin | Spanish fly | Ycanth }} |
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| CASNo = <!-- blanked - oldvalue: 56-25-7 --> |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|changed|??}} |
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| CASNo = 56-25-7 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = <!-- blanked - oldvalue: C16778 --> |
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| KEGG = C16778 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 236798 |
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| ChEMBL = 48449 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| ChEBI = 64213 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = IGL471WQ8P |
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| UNII = IGL471WQ8P |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 2297293 |
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| ChemSpiderID = 2297293 |
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| PubChem = 5944 |
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| EC_number = 200-263-3 |
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| Beilstein = 85302 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C10H12O4/c1-9-5-3-4-6(13-5)10(9,2)8(12)14-7(9)11/h5-6H,3-4H2,1-2H3/t5-,6+,9-,10+ |
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| StdInChI = 1S/C10H12O4/c1-9-5-3-4-6(13-5)10(9,2)8(12)14-7(9)11/h5-6H,3-4H2,1-2H3/t5-,6+,9-,10+ |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = DHZBEENLJMYSHQ-YUMGAWCOSA-N |
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| StdInChIKey = DHZBEENLJMYSHQ-YUMGAWCOSA-N |
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| SMILES = O=C2OC(1(C) 3CC(O3)12C)=O |
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| SMILES = O=C2OC(1(C)3CC(O3)12C)=O |
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}} |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=10 | H=12 | O=4 |
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| Formula = C<sub>10</sub>H<sub>12</sub>O<sub>4</sub> |
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| MolarMass = 196.20 g/mol |
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| Density = 1.41 g/cm<sup>3</sup> |
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| MeltingPtC = 212 |
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| Density = 1.41 g/cm³ |
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| MeltingPt = 212 °C |
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}} |
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| Section6 = {{Chembox Pharmacology |
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| ATCCode_prefix = None |
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| ATCvet = |
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| Legal_NZ = Class A |
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| Legal_US = Rx-only |
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| Legal_US_comment = <ref>{{cite web | title=Ycanth- cantharidin solution | website=DailyMed | date=25 July 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c9bdeaa-9822-4c69-a719-ea4a8643f59c | access-date=28 August 2023 | archive-date=29 August 2023 | archive-url=https://web.archive.org/web/20230829043322/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c9bdeaa-9822-4c69-a719-ea4a8643f59c | url-status=live }}</ref> |
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| Dependence_liability = |
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| AdminRoutes = Topical |
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|Section7={{Chembox Hazards |
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| MainHazards = Highly toxic |
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| GHSPictograms = {{GHS skull and crossbones}} {{GHS exclamation mark }} |
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| GHSSignalWord = Danger |
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| HPhrases = {{H-phrases|300|315|319|335}} |
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| PPhrases = {{P-phrases|261|264|270|271|280|301+310|302+352|304+340|305+351+338|312|321|330|332+313|337+313|362|403+233|405|501}} |
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| NFPA-H = 4 |
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| NFPA-F = 1 |
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| NFPA-R = 1 |
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| LD50 = 0.03–0.5 mg/kg (human)}} |
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}} |
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{{Infobox drug |
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| container_only = yes |
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| INN = |
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| type = <!-- empty --> |
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| image = |
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| alt = |
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| caption = |
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<!-- Clinical data --> |
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| pronounce = |
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| tradename = Ycanth, others |
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| Drugs.com = |
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| MedlinePlus = |
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| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) --> |
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| licence_EU = <!-- EMA uses INN (or special INN_EMA) --> |
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| DailyMedID = Cantharidin |
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| licence_US = <!-- FDA may use generic or brand name (generic name preferred) --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| routes_of_administration = ] |
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| ATC_prefix = <!-- 'none' if uncategorised --> |
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<!-- Legal status --> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Identifiers --> |
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| DrugBank = DB12328 |
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| C=10 | H=12 | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I= |
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}} |
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'''Cantharidin''' is an odorless, colorless fatty substance of the ] class, which is secreted by many species of ]s.{{efn|Including broadly in genus '']'', genus '']'', and in species ]. ], ], and ] also produce cantharidin.}} Its main current use in pharmacology is treating ] and ] topically.<ref>{{cite web | url=https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-molluscum-contagiosum | title=FDA approves first treatment for molluscum contagiosum | work=FDA | date=24 July 2023 }}</ref> It is a burn agent and ]ous in large doses, and has been historically used as ]s (]). In its natural form, cantharidin is secreted by the male blister beetle, and given to the female as a copulatory gift during mating. Afterwards, the female beetle covers her eggs with it as a defense against predators. |
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Poisoning from cantharidin is a significant veterinary concern, especially in horses, but it can also be poisonous to humans if taken internally (where the source is usually experimental self-exposure). Externally, cantharidin is a potent ] (blistering agent), exposure to which can cause severe ]s. Properly dosed and applied, the same properties have also been used therapeutically, for instance, for treatment of skin conditions, such as ] infection of the skin. |
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Cantharidin is classified as an ] in the ], and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.<ref>As defined in Section 302 of the U.S. ] (42 U.S.C. 11002). See {{Webarchive|url=https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf |date=25 February 2012 }} (PDF) (1 July 2008 ed.). U.S. Government Printing Office. Retrieved 29 October 2011.</ref> |
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==Chemistry== |
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===Structure and nomenclature=== |
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Cantharidin, from the Greek ''kantharis'', for beetle,<ref>{{cite book | title = A Dictionary of Entomology | date = 2011 | publisher = CABI | page = 253}}</ref> is an odorless, colorless ] with solubility in various organic solvents,{{specify|date=December 2015}} but only slight solubility in water.<ref name = veterinary>{{cite book | vauthors = Schmitz DG | veditors = Aiello SE, Moses MA | year = 2013 | title = The Merck Veterinary Manual | chapter = Overview of Cantharidin Poisoning (Blister Beetle Poisoning) | location = Kenilworth, NJ, USA | publisher = Merck Sharp & Dohme | isbn = 978-0911910612 | chapter-url = https://www.merckvetmanual.com/mvm/toxicology/cantharidin_poisoning/overview_of_cantharidin_poisoning.html | access-date = 14 December 2015 | archive-date = 22 December 2015 | archive-url = https://web.archive.org/web/20151222103819/https://www.merckvetmanual.com/mvm/toxicology/cantharidin_poisoning/overview_of_cantharidin_poisoning.html | url-status = dead }}</ref> Its skeleton is ], formally, a tricyclo-decane skeleton. Its functionalities include a ] (−CO−O−CO−) substructure in one of its rings, as well as a bridging ] in its ] ring system. |
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] |
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The complete mechanism of the ] of cantharidin is unknown. Its framework formally consists of two ] units.<ref>{{cite book | title = Secondary-Metabolite Biosynthesis and Metabolism | veditors = Petroski RJ, McCormick SP | publisher = Springer Science & Business Media | date = 2012 | isbn = 978-0-306-44309-1 }}</ref> However, ] indicate that the biosynthetic process is more complicated, and not a simple product of ] or related ten-carbon parent structure, as the seeming ] nature would suggest. Instead, there is a ] (15-carbon) precursor from which certain carbon segments are later excised.<ref>{{cite journal | vauthors = Jiang M, Lü S, Zhang Y | title = The Potential Organ Involved in Cantharidin Biosynthesis in Epicauta chinensis Laporte (Coleoptera: Meloidae) | journal = Journal of Insect Science | volume = 17 | issue = 2 | pages = 52 | date = January 2017 | pmid = 28423415 | pmc = 5633858 | doi = 10.1093/jisesa/iex021 }}</ref> |
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===Distribution and availability=== |
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The level of cantharidin in blister beetles can be quite variable. Among blister beetles of the genus '']'' in ], ''E. pennsylvanica'' contains about 0.2 mg, ''E. maculata'' contains 0.7 mg, and ''E. immaculata'' contains 4.8 mg per beetle; males also contain higher levels than females.<ref>{{cite journal | vauthors = Capinera JL, Gardner DR, Stermitz FR | title = Cantharidin Levels in Blister Beetles (Coleoptera: Meloidae) Associated with Alfalfa in Colorado | journal = Journal of Economic Entomology | year = 1985 | volume = 78 | issue = 5 | pages = 1052–1055 |doi=10.1093/jee/78.5.1052 }}</ref> |
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Males of '']'' have higher level of cantharidin per beetle: 64.22 ± 51.28 mg/g (dry weight) and 9.10 ± 12.64 mg/g (d. w.). Cantharidin content in ] is also higher in males (80.9 ± 106.5 μg/g) than in females (20.0 ± 41.5 μg/g).<ref name=Bravo2017>{{cite journal| vauthors = Bravo C, Mas-Peinado P, Bautista LM, Blanco G, Alonso JC, García-París M |title=Cantharidin is conserved across phylogeographic lineages and present in both morphs of Iberian ''Berberomeloe'' blister beetles (Coleoptera, Meloidae)|journal=Zoological Journal of the Linnean Society|year=2017|volume=180|issue=4|pages=790–804|doi=10.1093/zoolinnean/zlw016|hdl=10261/153832|hdl-access=free}}</ref> |
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==History== |
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]"), a beetle that secretes cantharidin.]] |
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===Aphrodisiac preparations=== |
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Preparations made from ]s (particularly "]") have been used since ancient times as an ], possibly because their physical effects were perceived to mimic those of sexual arousal,<ref>John L. Capinera, ''Encyclopedia of Entomology, Volume 4'', Springer Science & Business Media, 2008. p.2010</ref> and because they can cause prolonged erection or ] in men.<ref name = aph>Peter V. Taberner, ''Aphrodisiacs: The Science and the Myth'', Springer Science & Business Media, 2012, pp.100ff</ref> These preparations were known as ''cantharides'', from the Greek word for "beetle". |
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Examples of such use found in historical sources include: |
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* The ancient Roman historian ] relates that a cantharid preparation was used by the empress ], wife of ], to entice members of the imperial family or dinner guests to commit sexual indiscretions (thus, providing her information to hold over them).<ref>{{cite book|title = Ancient Inventions| vauthors = James P |publisher = Ballantine Books|isbn = 978-0-345-40102-1|year = 1995|page = |url = https://archive.org/details/ancientinvention00jame/page/177}}</ref> |
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* The German emperor ] (1050–1106) is said to have consumed cantharides.<ref>{{cite web | url=http://blogs.scientificamerican.com/guest-blog/2012/03/13/when-sparks-fly-aphrodisiacs-and-the-fruit-fly/ | title=When Sparks Fly: Aphrodisiacs and the Fruit Fly | work=Scientific American | date=13 March 2012 | access-date=18 November 2014 | vauthors=Eplett L | archive-date=29 November 2014 | archive-url=https://web.archive.org/web/20141129060929/http://blogs.scientificamerican.com/guest-blog/2012/03/13/when-sparks-fly-aphrodisiacs-and-the-fruit-fly/ | url-status=live }}</ref> |
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* The French surgeon ] (1510–1590) described a case in 1572 of a man suffering from "the most frightful ]" after taking a potion composed of ] and a cantharid extract.<ref name="Milsten_1">{{cite book | vauthors = Milsten R |title=The Sexual Male: Problems and Solutions|publisher=W. W. Norton & Company |year=2000 |isbn=978-0-393-32127-2 |page=170}}</ref> This is perhaps the same man of whom Paré relates that a ] sprinkled a cantharid powder on food she served to him, after which the man experienced "violent priapism" and anal bleeding, of which he later died. Paré also cites the case of a priest who died of ] after swallowing a dose of cantharides, which he intended to fortify his sex drive.<ref name = "Cabanès">{{cite book | author-link1 = Augustin Cabanès | vauthors = Cabanès A | url = https://archive.org/stream/b24878613#page/498/mode/2up | title = Remèdes d'autrefois | location = Paris | publisher = A. Maloine | date = 1910 | page = 498 }}</ref> |
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* Cantharides were in widespread use among the upper classes in France in the 1600s, despite being a banned substance. Police searches in connection with a rash of poisonings around 1680 turned up many stashes of "bluish flies", which were known to be used in the preparation of aphrodisiac potions.<ref name = "Cabanès"/> |
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* The French sorceress ] (known as "La Voisin," c. 1640–1680) was recorded in the 1670s as having prepared a love charm made from ] mixed with dried mole's blood and bat's blood.<ref>Richard Cavendish, ''The Black Arts'' (London: Pan Books, 1969), p. 333.<!--Can someone check the page number on this? It was inherited from a previous inaccurate form of the citation.--></ref> |
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* Aphrodisiac sweets presumably laced with cantharides were circulated within ] circles during the 1700s in France. They were multicolored tablets nicknamed "pastilles de Richelieu," after the ], a notorious libertine (not to be confused with his great-uncle, the ]) who procured sexual encounters for King ].<ref name = "Cabanès"/><ref>Jacques Levron, ''Le Maréchal de Richelieu, un libertin fastueux'' (Paris, Perrin, 1971).</ref> |
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* The French writer Donatien Alphonse François — notoriously known as the ] (1740–1814) — is said to have given ]-flavored pastilles laced with Spanish fly to two prostitutes at a pair of orgies in 1772, poisoning and nearly killing them. He was sentenced to death for that (and for the crime of ]), but was later reprieved on appeal.<ref name="isbn0-394-54797-7">{{cite book | vauthors = Ford P, Howell, Michael M |title=The beetle of Aphrodite and other medical mysteries |publisher=Random House |location=New York |year=1985 |isbn=978-0-394-54797-8 |url=https://archive.org/details/beetleofaphrodit00howe }}</ref><ref name = sch>{{cite book | vauthors = Schaeffer N | date = 2000 | title = The Marquis de Sade: A Life | location = Cambridge, MA, USA | publisher = Harvard University Press | page = 58 }}</ref> |
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===Non-aphrodisiac uses=== |
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* The Spanish clergyman ] (]) (c. 1540–1610) reported the use of blister beetles as a ] as well as an aphrodisiac.<ref name="Covarrubias_1">{{cite book |title =Tesoros de la lengua castellana o española | vauthors = Covarrubias-Horozco S |publisher = Universidad de Navarra - Iberoamericana - Vervuert |year = 2006 }}</ref> |
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* Preparations of dried blister beetles were at one time used as a treatment for ].<ref>{{cite book|vauthors=Closs JF|title=A New Method of Curing the Small-pox ... with a Specimen of Miscellaneous Observations on Medical Subjects; from the Latin ... by a Physician|url=https://books.google.com/books?id=HOtbAAAAcAAJ&pg=PA10|year=1767|publisher=Hawes|access-date=15 April 2017|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114162555/https://books.google.com/books?id=HOtbAAAAcAAJ&pg=PA10|url-status=live}} Cantharides referred to throughout the book.</ref> As late as 1892, ], the founder of ], recommended inhaling a ] of cantharidin as an effective preventative and treatment for smallpox, decrying ].<ref>Andrew Taylor Still, ''The philosophy and mechanical principles of osteopathy'', 1892, chapter 12: "Smallpox". The 1902 edition is {{Webarchive|url=https://web.archive.org/web/20190714030929/https://anatomy4beginners.com/resources/The%20Philosophy%20and%20Mechanical%20Principles%20of%20Osteopathy%20AT%20Still%201902.pdf |date=14 July 2019 }}.</ref> |
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===Pharmaco-chemical isolation=== |
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Cantharidin was first isolated as a chemically pure substance in 1810 by ],<ref>{{cite book | vauthors = Wolter H | year = 1995 | title = Kompendium der Tierärztlichen Homöopathie | publisher = Enke | isbn = 978-3432978925 }}</ref> a French chemist then living in ]. Robiquet isolated cantharidin as the active ingredient in pharmacological preparations of '']'', a.k.a. "]", a species of ]. This was one of the first historical instances of the identification and extraction of a simple active principle from a complex medicine. |
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Robiquet found cantharidin to be an odorless and colorless solid at ]. He demonstrated that it was the active principle responsible for the aggressively ] of the coating of the eggs of the blister beetle, and additionally established that cantharidin had toxic properties comparable in degree to those of the most virulent poisons known in the 19th century, such as ].<ref>{{cite journal | vauthors = Robiquet PJ | title = Expériences sur les cantharides | journal = Annales de Chimie | year = 1810 | volume = 76 | pages = 302–322 }}</ref> |
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===Other uses of the pharmacological isolate=== |
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* Diluted solutions of cantharidin can be used as a ] medication to remove ]s<ref name="pmid13519856">{{cite journal | vauthors = Epstein WL, Kligman AM | title = Treatment of warts with cantharidin | journal = A.M.A. Archives of Dermatology | volume = 77 | issue = 5 | pages = 508–511 | date = May 1958 | pmid = 13519856 | doi = 10.1001/archderm.1958.01560050014003 }}</ref><ref name="bacelieri">{{cite journal | vauthors = Bacelieri R, Johnson SM | title = Cutaneous warts: an evidence-based approach to therapy | journal = American Family Physician | volume = 72 | issue = 4 | pages = 647–652 | date = August 2005 | pmid = 16127954 | url = http://www.aafp.org/afp/20050815/647.html | access-date = 2 December 2012 | url-status = dead | archive-url = https://web.archive.org/web/20080709031002/http://www.aafp.org/afp/20050815/647.html | archive-date = 9 July 2008 }}</ref> and ]s, and to treat the small ] of '']''.<ref>{{cite web | title = Molluscum contagiosum | url = http://www.merck.com/mmpe/sec10/ch122/ch122b.html | date = November 2005 | publisher = Merck Manuals | access-date = 21 October 2007 | archive-date = 18 October 2007 | archive-url = https://web.archive.org/web/20071018055759/http://merck.com/mmpe/sec10/ch122/ch122b.html | url-status = live }}</ref> |
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* In ] rituals, cantharides are used in ].<ref name="Gonzalez-Wippler_1">{{cite book | vauthors = Gonzalez-Wippler M |title=Santería: The Religion |publisher=Llewellyn Publications |year=2002 |isbn=978-1-56718-329-0 |page= |url=https://archive.org/details/santerareligio00gonz/page/221 }}</ref> |
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==Veterinary issues== |
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Poisoning by ''Epicauta'' species from cantharidin is a significant veterinary concern, especially in horses; species infesting feedstocks depend on region—e.g., ''Epicauta pennsylvanica'' (black blister beetle) in the U.S. midwest; and ''E. occidentalis, temexia, and vittata'' species (striped blister beetles) in the U.S. southwest—where the concentrations of the agent in each can vary substantially.<ref name = veterinary/> Beetles feed on ]s, and occasionally move into crop fields used to produce livestock feeds (e.g., ]), where they are found to cluster and find their way into ], e.g., a single flake (4–5 in. section<ref>{{cite book | vauthors = Rockett J, Bosted S | year = 2015 | title = Veterinary Clinical Procedures in Large Animal Practices | publisher = Cengage Learning | isbn = 978-1305537651 | location = Boston, MA, USA | url = https://books.google.com/books?isbn=1305537653 | access-date = 14 December 2015 | page = 65}}</ref>) may have several hundred insects, or none at all.<ref name = veterinary/> Horses are very sensitive to the cantharidin produced by beetle infestations: the {{LD50}} for horses is roughly 1 mg/kg of the horse's body weight. Horses may be accidentally poisoned when fed bales of fodder with blister beetles in them.<ref>{{cite web | url = http://www.addl.purdue.edu/newsletters/2006/Fall/EquineCT.htm | title = Blister Beetle Poisoning / Cantharidin toxicosis | access-date = 31 December 2010 | archive-date = 26 June 2010 | archive-url = https://web.archive.org/web/20100626083233/https://www.addl.purdue.edu/newsletters/2006/Fall/EquineCT.htm | url-status = live }}</ref> |
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]s, a strongly ] bird species,<ref>{{cite journal|doi=10.1007/s00265-010-0972-6 |title=Correlates of male mating success in great bustard leks: the effects of age, weight, and display effort |year=2010 | vauthors = Alonso JC, Magaña M, Palacín C, Martín CA |journal=Behavioral Ecology and Sociobiology |volume=64 |issue=10 |pages=1589–1600|bibcode=2010BEcoS..64.1589A |hdl=10261/76985 |s2cid=8741416 }}</ref> are not immune to the toxicity of cantharidin; they become intoxicated after ingesting blister beetles. However, cantharidin has activity also against parasites that infect them.<ref>{{cite journal | vauthors = Bravo C, Bautista LM, García-París M, Blanco G, Alonso JC | title = Males of a strongly polygynous species consume more poisonous food than females | journal = PLOS ONE | volume = 9 | issue = 10 | pages = e111057 | year = 2014 | pmid = 25337911 | pmc = 4206510 | doi = 10.1371/journal.pone.0111057 | bibcode = 2014PLoSO...9k1057B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sánchez-Barbudo IS, Camarero PR, García-Montijano M, Mateo R | title = Possible cantharidin poisoning of a great bustard (Otis tarda) | journal = Toxicon | volume = 59 | issue = 1 | pages = 100–103 | date = January 2012 | pmid = 22001622 | doi = 10.1016/j.toxicon.2011.10.002 | bibcode = 2012Txcn...59..100S | hdl-access = free | hdl = 10261/143513 }}</ref> Great bustards may eat toxic ]s of the genus '']'' to increase the sexual arousal of males.<ref name=Heneberg2016>{{cite journal | vauthors = Heneberg P |title=On Otis tarda and Marquis de Sade: what motivates male Great Bustards to consume Blister Beetles (Meloidae)? |year=2016 |journal=Journal of Ornithology |volume=57 |issue=4 |pages=1123–1125 |doi=10.1007/s10336-016-1369-8|bibcode=2016JOrni.157.1123H |s2cid=17325635 }}</ref> |
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==Human medical issues== |
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===General risks=== |
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As a blister agent, cantharidin has the potential to cause adverse effects when used medically; for this reason, it has been included in a list of "problem drugs" used by dermatologists and emergency personnel.<ref name="karras-1996">{{cite journal | vauthors = Karras DJ, Farrell SE, Harrigan RA, Henretig FM, Gealt L | title = Poisoning from "Spanish fly" (cantharidin) | journal = The American Journal of Emergency Medicine | volume = 14 | issue = 5 | pages = 478–483 | date = September 1996 | pmid = 8765116 | doi = 10.1016/S0735-6757(96)90158-8 | quote = While most commonly available preparations of Spanish fly contain cantharidin in negligible amounts, if at all, the chemical is available illicitly in concentrations capable of causing severe toxicity. Symptoms of cantharidin poisoning include burning of the mouth, dysphagia, nausea, hematemesis, gross hematuria, and dysuria. Mucosal erosion and hemorrhage is seen in the upper gastrointestinal (GI) tract. Renal dysfunction is common and related to acute tubular necrosis and glomerular destruction. }}</ref> However, this references unregulated sources of cantharidin.<ref name="Binder-1979"> {{cite journal | vauthors = Binder R | title = Malpractice--in dermatology | journal = Cutis | volume = 23 | issue = 5 | pages = 663–666 | date = May 1979 | pmid = 456036 }}</ref> In July 2023, the US FDA approved a topical formulation of cantharidin (Ycanth) for the treatment of ].<ref>{{cite web | url = https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-molluscum-contagiosum | title = FDA approves first treatment for molluscum contagiosum | date = 24 July 2023 | work = U.S. Food and Drug Administration | access-date = 6 August 2023 | archive-date = 11 August 2023 | archive-url = https://web.archive.org/web/20230811031511/https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-molluscum-contagiosum | url-status = live }}</ref> |
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When ] by humans, the {{LD50}} is unknown, but fatal doses have been |
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recorded between 10 mg and 65 mg.<ref>{{cite journal | url=https://jamanetwork.com/journals/jamadermatology/fullarticle/478535 | doi=10.1001/archderm.137.10.1357 | title=Cantharidin Revisited | date=2001 | journal=Archives of Dermatology | volume=137 | issue=10 | pages=1357–1360 | pmid=11594862 | vauthors = Moed L, Shwayder TA, Chang MW }}</ref> The median lethal dose appears to be around 1 mg/kg<ref>{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/14428136/ | pmid=14428136 | date=1960 | author1=OAKS WW | author2=DITUNNO JF | author3=MAGNANI T | author4=LEVY HA | author5=MILLS LC | title=Cantharidin poisoning | journal=Archives of Internal Medicine | volume=105 | issue=4 | pages=574–582 | doi=10.1001/archinte.1960.00270160072009 }}</ref> but individuals have survived after consuming oral doses as high as 175 mg.<ref>{{cite journal | url=https://pubs.acs.org/doi/10.1021/jf00077a045 | doi=10.1021/jf00077a045 | title=Endothal and cantharidin analogs: Relation of structure to herbicidal activity and mammalian toxicity | date=1987 | journal=Journal of Agricultural and Food Chemistry | volume=35 | issue=5 | pages=823–829 | bibcode=1987JAFC...35..823M | vauthors = Matsuzawa M, Graziano MJ, Casida JE }}</ref> Ingesting cantharidin can initially cause severe damage to the lining of the ] and ], and may also cause permanent ] damage. Symptoms of cantharidin poisoning include ], abdominal pain, and (rarely) ].<ref name="Binder-1979" /> |
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===Risks of aphrodisiac use=== |
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{{main|Lytta vesicatoria}} |
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The extreme toxicity of cantharidin makes any use as an aphrodisiac highly dangerous.<ref name=shamloul-2010>{{cite journal | vauthors = Shamloul R | title = Natural aphrodisiacs | journal = The Journal of Sexual Medicine | volume = 7 | issue = 1 Pt 1 | pages = 39–49 | date = January 2010 | pmid = 19796015 | doi = 10.1111/j.1743-6109.2009.01521.x }}</ref><ref name=sandroni-2001>{{cite journal | vauthors = Sandroni P | title = Aphrodisiacs past and present: a historical review | journal = Clinical Autonomic Research | volume = 11 | issue = 5 | pages = 303–307 | date = October 2001 | pmid = 11758796 | doi = 10.1007/BF02332975 | quote = Cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which has been used for millennia as a sexual stimulant by both sexes. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of β-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The gastrointestinal tract sustains the brunt of toxicity, resulting in fatal hemorrhages. Renal toxicity is a result of its renal excretion, which may lead to acute tubular necrosis. Cardiac effects are most likely due to hemorrhagic shock, but they also can be due to myofibril degeneration, mitochondrial swelling, and pericardial and subendocardial hemorrhages. | s2cid = 32348540 }}</ref> As a result, it is illegal to sell (or use) cantharidin or preparations containing it without a prescription in many countries.<ref name=karras-1996/> |
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==Research== |
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===Mechanism of action=== |
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{{missing information|section|toxicological mechanism when ingested|date=September 2022}} |
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Topical cantharidin is absorbed by the lipid membranes of ], causing the release of ], ] that break the ] in proteins. This causes the disintegration of ], cellular structures involved in cell-to-cell adhesion, leading to detachment of the ] that hold cells together. The process leads to the loss of cellular connections (]), and ultimately results in blistering of the skin. Lesions heal without scarring.<ref name=Moed2001>{{cite journal | vauthors = Moed L, Shwayder TA, Chang MW | title = Cantharidin revisited: a blistering defense of an ancient medicine | journal = Archives of Dermatology | volume = 137 | issue = 10 | pages = 1357–1360 | date = October 2001 | pmid = 11594862 | doi = 10.1001/archderm.137.10.1357 | doi-access = free }}</ref><ref name=Bertaux1988>{{cite journal | vauthors = Bertaux B, Prost C, Heslan M, Dubertret L | title = Cantharide acantholysis: endogenous protease activation leading to desmosomal plaque dissolution | journal = The British Journal of Dermatology | volume = 118 | issue = 2 | pages = 157–165 | date = February 1988 | pmid = 3279999 | doi = 10.1111/j.1365-2133.1988.tb01769.x | s2cid = 45714898 }}</ref> |
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===Pharmaceutical use=== |
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VP-102, an experimental drug-device combination that includes cantharidin delivered via a single-use applicator, is being studied for the treatment of ], ], and ]s.<ref>{{cite news | url = https://www.drugs.com/nda/vp_102_210528.html | title = Verrica Pharmaceuticals Announces Extension of FDA Review Period of its NDA for VP-102 for the Treatment of Molluscum Contagiosum | date = 28 May 2021 | publisher = ] | access-date = 24 June 2021 | archive-date = 24 June 2021 | archive-url = https://web.archive.org/web/20210624205303/https://www.drugs.com/nda/vp_102_210528.html | url-status = live }}</ref> |
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===Bioactivities=== |
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Cantharidin appears to have some effect in the topical treatment of ] in animal models.<ref>{{cite journal | vauthors = Ghaffarifar F | title = Leishmania major: in vitro and in vivo anti-leishmanial effect of cantharidin | journal = Experimental Parasitology | volume = 126 | issue = 2 | pages = 126–129 | date = October 2010 | pmid = 20435039 | doi = 10.1016/j.exppara.2010.04.004 | doi-access = free }}</ref> In addition to topical medical applications, cantharidin and its analogues may have activity against cancer cells.<ref>{{cite journal | vauthors = Ratcliffe NA, Mello CB, Garcia ES, Butt TM, Azambuja P | title = Insect natural products and processes: new treatments for human disease | journal = Insect Biochemistry and Molecular Biology | volume = 41 | issue = 10 | pages = 747–769 | date = October 2011 | pmid = 21658450 | doi = 10.1016/j.ibmb.2011.05.007 | bibcode = 2011IBMB...41..747R }}</ref><ref>{{cite journal | vauthors = Chen YN, Cheng CC, Chen JC, Tsauer W, Hsu SL | title = Norcantharidin-induced apoptosis is via the extracellular signal-regulated kinase and c-Jun-NH2-terminal kinase signaling pathways in human hepatoma HepG2 cells | journal = British Journal of Pharmacology | volume = 140 | issue = 3 | pages = 461–470 | date = October 2003 | pmid = 12970086 | pmc = 1574052 | doi = 10.1038/sj.bjp.0705461 }}</ref><ref>{{cite journal | vauthors = Zhang C, Peng Y, Wang F, Tan X, Liu N, Fan S, Wang D, Zhang L, Liu D, Wang T, Wang S, Zhou Y, Su Y, Cheng T, Zhuang Z, Shi C | title = A synthetic cantharidin analog for the enhancement of doxorubicin suppression of stem cell-derived aggressive sarcoma | journal = Biomaterials | volume = 31 | issue = 36 | pages = 9535–9543 | date = December 2010 | pmid = 20875681 | doi = 10.1016/j.biomaterials.2010.08.059 }}</ref> |
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Laboratory studies with cultured tumor cells suggest that this activity may be the result of ] inhibition.<ref>{{cite journal | vauthors = Dorn DC, Kou CA, Png KJ, Moore MA | title = The effect of cantharidins on leukemic stem cells | journal = International Journal of Cancer | volume = 124 | issue = 9 | pages = 2186–2199 | date = May 2009 | pmid = 19123473 | doi = 10.1002/ijc.24157 | s2cid = 38088568 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z, Han X | title = Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis | journal = Cancer Science | volume = 101 | issue = 5 | pages = 1226–1233 | date = May 2010 | pmid = 20331621 | doi = 10.1111/j.1349-7006.2010.01523.x | s2cid = 24345174 | doi-access = free | pmc = 11158714 }}</ref> |
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== Notes == |
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{{notelist}} |
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== References == |
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{{reflist}} |
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== External links == |
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* at Lycée Faidherbe de Lille |
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