Diprenorphine: Difference between revisions

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}

| Verifiedfields = changed

| verifiedrevid = 460793422

| IUPAC_name = (5α,7α)-17-(Cyclopropylmethyl)- 4,5-epoxy- 18,19-dihydro- 3-hydroxy- 6-methoxy- α,α-dimethyl- 6,14-ethenomorphinan- 7-methanol

| image = Diprenorphine.svg

| width = 225px

<!--Clinical data-->| tradename = Revivon

| Drugs.com = {{drugs.com|international|diprenorphine}}

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| pregnancy_US =

| pregnancy_category =

| legal_AU =

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| legal_US =

| legal_status =

| routes_of_administration = <!--Pharmacokinetic data-->

| bioavailability =

| protein_bound =

| metabolism =

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| excretion = <!--Identifiers-->

| CAS_number_Ref =

| CAS_number = 14357-78-9

| ATCvet = yes

| ATC_prefix = V03

| ATC_suffix = AB92

| PubChem = 443408

| IUPHAR_ligand = 1617

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01548

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 391634

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 1F0L5N25ZZ

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D07863

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 281786

| synonyms = Diprenorfin; M5050

<!--Chemical data-->| C = 26

| H = 35

| N = 1

| O = 4

| SMILES = CC(C)([C@H]1C[C@@]23CC[C@@]1([C@H]4[C@@]25CCN([C@@H]3CC6=C5C(=C(C=C6)O)O4)CC7CC7)OC)O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C26H35NO4/c1-23(2,29)18-13-24-8-9-26(18,30-3)22-25(24)10-11-27(14-15-4-5-15)19(24)12-16-6-7-17(28)21(31-22)20(16)25/h6-7,15,18-19,22,28-29H,4-5,8-14H2,1-3H3/t18-,19-,22-,24-,25+,26-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = OIJXLIIMXHRJJH-KNLIIKEYSA-N

'''Diprenorphine''' (brand name '''Revivon'''; former developmental code name '''M5050'''),<ref>{{cite patent | country = US | number = 3433791 | title = Endoethano Nor Oripavines & Nor Thebaines }}</ref> also known as '''diprenorfin''', is a [[binding selectivity|non-selective]], high-[[affinity (pharmacology)|affinity]], weak [[partial agonist]] of the [[μ-opioid receptor|μ-]] (MOR), [[κ-opioid receptor|κ-]] (KOR), and [[δ-opioid receptor]] (DOR) (with equal affinity) which is used in [[veterinary medicine]] as an [[opioid antagonist]].<ref name="pmid15032698">{{cite journal | vauthors = Lewis JW, Husbands SM | title = The orvinols and related opioids--high affinity ligands with diverse efficacy profiles | journal = Current Pharmaceutical Design | volume = 10 | issue = 7 | pages = 717–32 | date = 2004 | pmid = 15032698 | doi = 10.2174/1381612043453027 }}</ref><ref name="BiegonVolkow1995">{{cite book| vauthors = Biegon A, Volkow ND |title=Sites of Drug Action in the Human Brain|url=https://archive.org/details/sitesofdrugactio00bieg|url-access=registration|date=24 February 1995|publisher=CRC Press|isbn=978-0-8493-7653-5|pages=[https://archive.org/details/sitesofdrugactio00bieg/page/149 149]–}}</ref><ref name="ShorvonPerucca2008">{{cite book| vauthors = Shorvon SD, Perucca E, Fish D, Dodson WE |title=The Treatment of Epilepsy|url=https://books.google.com/books?id=vFQFePTM-oAC&pg=PA657|date=15 April 2008|publisher=John Wiley & Sons|isbn=978-0-470-75245-6|pages=657–}}</ref> It is used to reverse the effects of super-potent [[opioid]] [[analgesic]]s such as [[etorphine]] and [[carfentanil]] that are used for [[tranquilizer|tranquilizing]] large animals. The drug is not approved for use in humans.<ref name="ClarkeTrim2013">{{cite book| vauthors = Clarke KW, Trim CM |title=Veterinary Anaesthesia|url=https://books.google.com/books?id=hZh5AAAAQBAJ&pg=PA93|date=28 June 2013|publisher=Elsevier Health Sciences|isbn=978-0-7020-5423-5|pages=93–}}</ref>

Diprenorphine is the strongest opioid antagonist that is commercially available (some 100 times more potent as an antagonist than [[nalorphine]]),<ref>{{cite journal | vauthors = Furst S, Hosztafi S, Friedmann T | title = Structure-Activity Relationships of Synthetic and Semisynthetic Opioid Agonists and Antagonists. | journal = Current Medicinal Chemistry | date = 1995 | volume = 1 | issue = 6 | pages = 423–440 | doi = 10.2174/092986730106220216112120 | s2cid = 99996951 }}</ref> and is used for reversing the effects of very strong opioids for which the binding affinity is so high that [[naloxone]] does not effectively or reliably reverse the narcotic effects.<ref>{{cite journal | vauthors = Takemori AE, Hayashi G, Smits SE | title = Studies on the quantitative antagonism of analgesics by naloxone and diprenorphine | journal = European Journal of Pharmacology | volume = 20 | issue = 1 | pages = 85–92 | date = October 1972 | pmid = 4637947 | doi = 10.1016/0014-2999(72)90219-1 }}</ref> These super-potent opioids, with the single exception of [[buprenorphine]] (which has an improved safety-profile due to its partial agonism character<ref>{{cite web | url = https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine | work = SAMHSA.gov | title = Medication Assisted Treatment | date = September 2015 | volume = 25 | issue = 1 | pages = 1 }}</ref>), are not used in humans because the dose for a human is so small that it would be difficult to measure properly {{citation needed|reason=see talk page|date=August 2018}}, so there is an excessive risk of [[overdose]] leading to fatal [[respiratory depression]]. However conventional opioid derivatives are not strong enough to rapidly tranquilize large animals, like elephants and rhinos, so drugs such as etorphine and carfentanil are available for this purpose.

Diprenorphine is considered to be the specific reversing agent/antagonist for etorphine and carfentanil,<ref name="pmid4077657">{{cite journal | vauthors = Jessup DA, Clark WE, Jones KR, Clark R, Lance WR | title = Immobilization of free-ranging desert bighorn sheep, tule elk, and wild horses, using carfentanil and xylazine: reversal with naloxone, diprenorphine, and yohimbine | journal = Journal of the American Veterinary Medical Association | volume = 187 | issue = 11 | pages = 1253–4 | date = December 1985 | pmid = 4077657 }}</ref> and is normally used to remobilise animals once veterinary procedures have been completed.<ref name="pmid4817959">{{cite journal | vauthors = Alford BT, Burkhart RL, Johnson WP | title = Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals | journal = Journal of the American Veterinary Medical Association | volume = 164 | issue = 7 | pages = 702–5 | date = April 1974 | pmid = 4817959 }}</ref> Since diprenorphine also has partial agonistic properties of its own, it should not be used on humans if they are accidentally exposed to etorphine or carfentanil. Naloxone or naltrexone is the preferred human opioid receptor antagonist.<ref>{{cite book | vauthors = Caulkett NA, Arnemo JM | chapter = Chemical Immobilization of Free-Ranging Terrestrial Mammals. | veditors = Tranquilli WJ, Thurmon JC, Grimm KA | title = Lumb and Jones' Veterinary Anesthesia and Analgesia. | edition = 4th | location = Philadelphia | publisher = Lippincott, Williams and Wilkins | date = 2007 | page = 815 }}</ref>

In theory, diprenorphine could also be used as an antidote for treating overdose of certain opioid derivatives which are used in humans, particularly [[buprenorphine]] for which the binding affinity is so high that naloxone does not reliably reverse the narcotic effects. However, diprenorphine is not generally available in hospitals; instead a vial of diprenorphine is supplied with etorphine or carfentanil specifically for reversing the effects of the drug, so the use of diprenorphine for treating a buprenorphine overdose is not usually carried out in practice.

Because diprenorphine is a weak partial agonist of the [[opioid receptor]]s rather than a [[silent antagonist]], it can produce some opioid effects in the absence of other opioids at sufficient doses.<ref name="WolfensohnLloyd2008">{{cite book| vauthors = Wolfensohn S, Lloyd M |title=Handbook of Laboratory Animal Management and Welfare|url=https://books.google.com/books?id=xVqjrZ7yQ2cC&pg=PA110|date=15 April 2008|publisher=John Wiley & Sons|isbn=978-1-4051-4777-4|pages=110–}}</ref> Moreover, due to partial agonism of the KOR, where it appears to possess significantly greater [[intrinsic activity]] relative to the MOR, diprenorphine can produce [[sedation]] as well as, in humans, [[hallucination]]s.<ref name="BiegonVolkow1995"/><ref name="ClarkeTrim2013" /><ref name="MillerFowler2011">{{cite book| vauthors = Miller RE, Fowler ME |title=Fowler's Zoo and Wild Animal Medicine Current Therapy|url=https://books.google.com/books?id=18A5OdzUBqEC&pg=PT1863|date=11 July 2011|publisher=Elsevier Health Sciences|isbn=978-1-4377-1985-7|pages=1863–}}</ref><ref name="Harrie1998">{{cite book| first = Louie S. | last = Harrie | title=Problems of Drug Dependence: 1996 Proceedings of the 59th Annual Scientific Symposium|url=https://books.google.com/books?id=uWA1LhDt-tQC&pg=PA155|date=1 July 1998|publisher=DIANE Publishing|isbn=978-0-7881-8130-6|pages=155–}}</ref><ref name="pmid3038579">{{cite journal | vauthors = Traynor JR, Corbett AD, Kosterlitz HW | title = Diprenorphine has agonist activity at opioid kappa-receptors in the myenteric plexus of the guinea-pig ileum | journal = European Journal of Pharmacology | volume = 137 | issue = 1 | pages = 85–9 | date = May 1987 | pmid = 3038579 | doi = 10.1016/0014-2999(87)90185-3 }}</ref>

{{Reflist}}

{{Opioid receptor modulators}}

[[Category:Delta-opioid receptor antagonists]]

[[Category:Kappa-opioid receptor agonists]]

[[Category:Kappa-opioid receptor antagonists]]

[[Category:4,5-Epoxymorphinans]]

[[Category:Mu-opioid receptor antagonists]]

[[Category:Tertiary alcohols]]