Diprenorphine

Diprenorphine

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
Pregnancy cat.	?
Legal status	Schedule II (US)
Identifiers
CAS number	14357-78-9 N
ATCvet code	QV03AB92
PubChem	CID 443408
DrugBank	DB01548
ChemSpider	391634 Y
UNII	1F0L5N25ZZ Y
KEGG	D07863 Y
ChEMBL	CHEMBL281786 Y
Chemical data
Formula	C26H35NO4
Mol. mass	425.56 g/mol
SMILES	eMolecules & PubChem
InChI 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 Y Key:OIJXLIIMXHRJJH-KNLIIKEYSA-N Y
N(what is this?)  (verify)

Diprenorphine (diprenorfin, Revivon, M5050)^[1] is an opioid antagonist^[2] used to reverse the effects of the super-potent opioid analgesics such as etorphine and carfentanil that are used for tranquilizing large animals in veterinary medicine.

Diprenorphine is the strongest opiate antagonist that is commercially available (some 100 times more potent as an antagonist than nalorphine),^[3] 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.^[4] These super-potent opioids 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,^[5] and is normally used to remobilise animals once veterinary procedures have been completed,^[6]. 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^[7].

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, 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 carried out in practice, although it would work in theory.

Legal status

Diprenorphine is a Schedule II drug in the USA.

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. ^ 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
4. ^ 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.
5. ^ 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.
6. ^ 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.
7. ^ 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.