{{Short description|Semi-synthetic opioid}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464368152 | IUPAC_name = (5α,6β,14β,18R)-18-[(2''R'')-2-Hydroxy-2-pentanyl]-6-methoxy-17-methyl-7,8-didehydro-18,19-dihydro-4,5-epoxy-6,14-ethenomorphinan-3-ol | image = Etorphine.svg | width = 150 | image_class = skin-invert-image | image2 = Etorphine-3D.png | image_class2 = bg-transparent | width2 = 150 <!--Clinical data-->| tradename = | Drugs.com = {{drugs.com|international|etorphine}} | legal_AU = S9 | legal_BR = F1 | legal_CA = Schedule I | legal_DE = Anlage III | legal_EU = List I | legal_EU_comment = (Netherlands) | legal_UK = Class A | legal_US = Schedule I | legal_US_comment = and Schedule II | legal_UN = N I IV
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'''Etorphine''' ('''M99''') is a semi-synthetic opioid possessing an analgesic potency approximately 1,000–3,000 times that of morphine.<ref name="pmid6042764">{{cite journal | vauthors = Bentley KW, Hardy DG | title = Novel analgesics and molecular rearrangements in the morphine-thebaine group. 3. Alcohols of the 6,14-endo-ethenotetrahydrooripavine series and derived analogs of N-allylnormorphine and -norcodeine | journal = Journal of the American Chemical Society | volume = 89 | issue = 13 | pages = 3281–3292 | date = June 1967 | pmid = 6042764 | doi = 10.1021/ja00989a032 | bibcode = 1967JAChS..89.3281B }}</ref> It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather the related plants ''Papaver orientale'' and ''Papaver bracteatum''.<ref name="urlOpium: the king of narcotics">{{cite book | chapter = Chapter 3 Opium: the king of narcotics | chapter-url = http://opioids.com/narcotic-drugs/chapter-3.html | title = Narcotic Drugs | vauthors = Aggrawal A | year = 1995 | publisher = National Book Trust | location = New Delhi | pages = xvi+161 | isbn = 81-237-1383-5 }}</ref> It was reproduced in 1963 by a research group at MacFarlan Smith in Edinburgh, led by Kenneth Bentley.<ref>{{cite journal |vauthors=Bentley KW, Hardy DG | title = New potent analgesics in the morphine series | journal = Proceedings of the Chemical Society | year = 1963 | volume = 220 | pages = 189–228 | doi = 10.1039/PS9630000189 }}</ref> It can be produced from thebaine.<ref>{{Cite journal | vauthors = Huang XR, Srimurugan S, Lee GH, Chen C |date=February 2011 |title=A Facile Synthesis and Structural Verification of Etorphine and Dihydroetorphine from Codeine |journal=Journal of the Chinese Chemical Society |volume=58 |issue=1 |pages=101–107 |doi=10.1002/jccs.201190048 |issn=0009-4536|doi-access=free }}</ref>
== Veterinary use == Etorphine is available legally only for veterinary use and is strictly governed by law. It is often used to immobilise elephants and other large mammals. Diprenorphine (Revivon) is an opioid receptor antagonist that can be administered in proportion to the amount of etorphine used (1.3 times) to reverse its effects. Veterinary-strength etorphine is fatal to humans. For this reason the package as supplied to vets always includes the human antidote along with the etorphine.
The human antidote is generally naloxone, not diprenorphine, and is always prepared before the preparation of etorphine to be immediately administered following accidental human exposure to etorphine. The {{LD50}} in humans is 3 μg {{Citation needed|date=December 2025}} which led to the requirement that the medicine include an equivalent dose of an antidote.
One of its main advantages is its speed of operation, and more importantly, the speed that diprenorphine reverses its effects. The high incidence of side effects, including severe cardiopulmonary depression, has caused etorphine to fall into disfavor in general veterinary practice. However, its high potency, combined with the rapid action of both etorphine and its antagonist, diprenorphine, means that it has found a place for use in the capture of large mammals, such as rhinoceroses and elephants, where rapid onset and rapid recovery are both very important. The high potency of etorphine means that sufficient etorphine can be administered to large wild mammals by projectile syringe (dart).
'''Large Animal Immobilon''' is a combination of etorphine plus acepromazine maleate. An etorphine antidote '''Large Animal Revivon''' contains mainly diprenorphine for animals and a human-specific naloxone-based antidote, which should be prepared prior to the etorphine. A 5–15 mg dose is enough to immobilise an African elephant and a 2–4 mg dose is enough to immobilise a black rhinoceros.<ref name="url_Zoo_Pharm">{{cite web | url = http://wildpharm.com/etorphine-hydrochloride-1mgml.html | title = Etorphine HCl | work = Veterinary medicine for wildlife: immobilisation medicine for animals zoo animals | publisher = Zoo Pharm | access-date = 2013-10-11 | archive-date = 2016-09-08 | archive-url = https://web.archive.org/web/20160908005713/http://wildpharm.com/etorphine-hydrochloride-1mgml.html | url-status = dead }}</ref>
== Pharmacology == Etorphine is a potent, non-selective full agonist of the μ-, δ-, and κ-opioid receptors.<ref name="Pasternak2013">{{cite book| vauthors = Pasternak G |title=The Opiate Receptors|url=https://books.google.com/books?id=vhfyBwAAQBAJ&pg=PA444|date=17 April 2013|publisher=Springer Science & Business Media|isbn=978-1-60761-990-1|pages=444–}}</ref><ref name="GharagozlouHashemi2006">{{cite journal | vauthors = Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J | title = Pharmacological profiles of opioid ligands at kappa opioid receptors | journal = BMC Pharmacology | volume = 6 | issue = 1 | article-number = 3 | date = January 2006 | pmid = 16433932 | pmc = 1403760 | doi = 10.1186/1471-2210-6-3 | doi-access = free }}</ref> It has a weak affinity for the nociceptin receptor.<ref name="pmid10688973">{{cite journal | vauthors = Hawkinson JE, Acosta-Burruel M, Espitia SA | title = Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors | journal = European Journal of Pharmacology | volume = 389 | issue = 2–3 | pages = 107–114 | date = February 2000 | pmid = 10688973 | doi = 10.1016/S0014-2999(99)00904-8 }}</ref>
== Legal status == In Hong Kong, etorphine is regulated under Schedule 1 of Chapter 134 of the ''Dangerous Drugs Ordinance''. It can be used legally only by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined HKD$10,000. The penalty for trafficking or manufacturing the substance is a HKD$5,000,000 fine and life imprisonment. Possession for consumption without licence from the Department of Health is illegal, with a HKD$1,000,000 fine and/or 7 years of jail time.<ref>{{Cite web |title=Hong Kong e-Legislation |url=https://www.elegislation.gov.hk/checkconfig/checkClientConfig.jsp?applicationId=RA001 |access-date=2022-03-30 |website=www.elegislation.gov.hk}}</ref>
In the Netherlands etorphine is a Schedule I drug of the Opium Law. It is used only for veterinary purposes in zoos to immobilise large animals.<ref>{{Cite web | work = Ministerie van Binnenlandse Zaken en Koninkrijksrelaties|title=Opiumwet |url=https://wetten.overheid.nl/BWBR0001941/2021-10-28#BijlageI |access-date=2022-03-30 |language=nl}}</ref>
In the United States etorphine is listed as a Schedule I (i.e. as not having any legal use) drug with an ACSCN of 9056, although its hydrochloride salt is classified as Schedule II (i.e. as having a legal use, such as tranquilization of large animals) with an ACSCN of 9059.<ref>{{Cite web | title = Etorphine | work = PubChem | id = CID 26721 |url=https://pubchem.ncbi.nlm.nih.gov/compound/26721 |access-date=2022-03-30 | publisher = U.S. National Library of Medicine |language=en}}</ref>
In the United Kingdom, under the Misuse of Drugs Act 1971, etorphine is controlled as a Class A substance.<ref>{{Cite web |title=List of most commonly encountered drugs currently controlled under the misuse of drugs legislation |url=https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation |access-date=2022-03-30 |website=GOV.UK |language=en}}</ref>
In Italy etorphine is illegal, as are the parent compounds Dihydroetorphine and Acetorphine. (Data from 2022)<ref>{{Cite web | work = Ministero della Salute |title=Tabelle delle sostanze stupefacenti e psicotrope |url= https://www.salute.gov.it/portale/medicinaliStupefacenti/dettaglioContenutiMedicinaliStupefacenti.jsp?lingua=italiano&id=3729&area=sostanzeStupefacenti&menu=vuoto&tab=1 |access-date=2022-04-09 |language=IT}}</ref>
== In popular culture == * The fictional character Dexter Morgan uses Etorphine M-99 to capture and sedate his victims in the television series, ''Dexter'', although this was retroactively changed to ketamine in the sequel series, ''Dexter: New Blood'', only for etorphine to return in the succeeding series, ''Dexter: Original Sin'' and ''Dexter: Resurrection''. * In the film ''The Meg'' etorphine is used to neutralise the first megalodon. * The fictional character Katherine Dutta uses etorphine to murder her victims in the television series ''Lewis'', [https://www.imdb.com/title/tt2412968/ Lewis: Down Among the Fearful]. * In an Agatha Raisin book, a fictional veterinarian is murdered with the Immobilon he planned to use to sedate a horse for an operation.
== See also == * 6,14-Endoethenotetrahydrooripavine - the central nucleus of all Bentley compound opioids under which class etorphine falls * 7-PET * Dihydroetorphine – a close analog of etorphine that has been used as an opioid painkiller for human use in China * Thienorphine * Opioid potency comparison
== References == {{Reflist|30em}}
== External links == * [http://opioids.com/etorphine/immobilon.html Opioids.com] page on etorphine * [http://www.chm.bris.ac.uk/motm/etorphine/etorphinec.htm Etorphine: Molecule of the Month]
{{Opioidergics}}
Category:Analgesics Category:Delta-opioid receptor agonists Category:4,5-Epoxymorphinans Category:Ethers Category:Semisynthetic opioids Category:Kappa-opioid receptor agonists Category:Mu-opioid receptor agonists Category:Nociceptin receptor agonists Category:Hydroxyarenes Category:Tertiary alcohols