Diprenorphine

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Diprenorphine
Diprenorphine.svg
Systematic (IUPAC) name
(5α,7α)-17-(Cyclopropylmethyl)- 4,5-epoxy- 18,19-dihydro- 3-hydroxy- 6-methoxy- α,α-dimethyl- 6,14-ethenomorphinan- 7-methanol
Clinical data
AHFS/Drugs.com International Drug Names
Identifiers
CAS Number 14357-78-9 N
ATCvet code QV03AB92 (WHO)
PubChem CID: 443408
IUPHAR/BPS 1617
DrugBank DB01548 YesY
ChemSpider 391634 YesY
UNII 1F0L5N25ZZ YesY
KEGG D07863 YesY
ChEMBL CHEMBL281786 YesY
Chemical data
Formula C26H35NO4
Molecular mass 425.56 g/mol
  • 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
  • InChI=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 YesY
  • Key:OIJXLIIMXHRJJH-KNLIIKEYSA-N YesY
 NYesY (what is this?)  (verify)

Diprenorphine (brand name Revivon; former developmental code name M5050),[1] also known as diprenorfin, is a non-selective, high-affinity, weak partial agonist of the μ- (MOR), κ- (KOR), and δ-opioid receptor (DOR) (with equal affinity) that is employed in veterinary medicine as an opioid antagonist.[2][3][4] It is used to reverse the effects of super-potent opioid analgesics such as etorphine and carfentanil that are used for tranquilizing large animals. The drug is not approved for use in humans.[5]

Diprenorphine is the strongest opioid antagonist that is commercially available (some 100 times more potent as an antagonist than nalorphine),[6] 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.[7] These super-potent opioids, with the single exception of buprenorphine (which has an improved safety-profile due to its partial agonism character[8]), are not used in humans because the dose for a human is so small that it would be difficult to measure properly, 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 such as elephants and rhinos, so drugs such as etorphine or carfentanil are available for this purpose.

Diprenorphine is considered the specific antagonist for etorphine and carfentanil,[9] and is normally used to remobilise animals once veterinary procedures have been completed.[10] Because diprenorphine also has some agonistic properties of its own, it should not be used on humans in the event that they are accidentally exposed to etorphine or carfentanil. Naloxone or naltrexone are the preferred human antagonists.[11]

In theory, diprenorphine could also be used as an antidote for treating overdose of certain opioid derivatives which are used in humans, such as buprenorphine (which has an improved safety-profile due to its partial agonism character), 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 these drugs, so use of diprenorphine for treating e.g. a buprenorphine overdose is not usually carried out in practice.

Because diprenorphine is a weak partial agonist of the opioid receptors rather than a silent antagonist, it can produce some opioid effects in the absence of other opioids at sufficient doses.[12] 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, hallucinations.[3][5][13][14][15]

See also

References

  1. ↑ US Patent 3433791 - Endoethano Nor Oripavines & Nor Thebaines
  2. ↑ Lewis JW, Husbands SM. The orvinols and related opioids--high affinity ligands with diverse efficacy profiles. Current Pharmaceutical Design. 2004;10(7):717-32.
  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Furst S, Hosztafi S, Friedmann T. Structure-Activity Relationships of Synthetic and Semisynthetic Opioid Agonists and Antagonists. Current Medicinal Chemistry, 1995; 1(6):423-440. ISSN 0929-8673
  7. ↑ Takemori AE, Hayashi G, Smits SE. Studies on the quantitative antagonism of analgesics by naloxone and diprenorphine. European Journal of Pharmacology. 1972 Oct;20(1):85-92. Abstract.
  8. ↑ SAMHSA.gov, Medication Assisted Treatment 2015 Sept.;25(1):1
  9. ↑ Jessup DA, Clark WE, Jones KR, Clark R, Lance WR. Immobilization of free-ranging desert bighorn sheep, tule elk, and wild horses, using carfentanil and xylazine: reversal with naloxone, diprenorphine, and yohimbine. Journal of the American Veterinary Medical Association. 1985 Dec 1;187(11):1253-4.
  10. ↑ Alford BT, Burkhart RL, Johnson WP. Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals. Journal of the American Veterinary Medical Association. 1974 Apr 1;164(7):702-5.
  11. ↑ Caulkett NA, Arnemo JM. Chemical Immobilization of Free-Ranging Terrestrial Mammals. In: Tranquilli WJ, Thurmon JC, Grimm KA, eds. Lumb and Jones' Veterinary Anesthesia and Analgesia. 4th ed. Philadelphia: Lippincott, Williams and Wilkins, 2007. 815.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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