:Kelatorphan
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = N-[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-L-alanine
| image = Kelatorphan.svg
| CAS_number = 92175-57-0
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 46BBW2U5D6
| ATC_prefix = None
| ATC_suffix =
| PubChem = 123982
| DrugBank = DB08040
| ChemSpiderID = 110501
| C = 14 | H = 18 | N = 2 | O = 5
| smiles = O=C(O)[C@@H](NC(=O)[C@H](Cc1ccccc1)CC(=O)NO)C
| StdInChI = 1S/C14H18N2O5/c1-9(14(19)20)15-13(18)11(8-12(17)16-21)7-10-5-3-2-4-6-10/h2-6,9,11,21H,7-8H2,1H3,(H,15,18)(H,16,17)(H,19,20)/t9-,11+/m0/s1
| StdInChIKey = OJCFZTVYDSKXNM-GXSJLCMTSA-N
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_category =
| legal_status = Non-regulated
| routes_of_administration =
}}
Kelatorphan is a drug which acts as a powerful and complete inhibitor of nearly all of the enzymes responsible for catabolism of the endogenous enkephalins, including neutral endopeptidase (NEP), dipeptidyl peptidase III (DPP3), aminopeptidase N (APN), and angiotensin-converting enzyme (ACE).{{cite journal | vauthors = Fournie-Zaluski MC, Chaillet P, Bouboutou R, Coulaud A, Cherot P, Waksman G, Costentin J, Roques BP | display-authors = 6 | title = Analgesic effects of kelatorphan, a new highly potent inhibitor of multiple enkephalin degrading enzymes | journal = European Journal of Pharmacology | volume = 102 | issue = 3–4 | pages = 525–528 | date = July 1984 | pmid = 6386492 | doi = 10.1016/0014-2999(84)90575-2 }}{{cite journal | vauthors = Yamamoto Y, Ono H, Ueda A, Shimamura M, Nishimura K, Hazato T | title = Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation | journal = Current Protein & Peptide Science | volume = 3 | issue = 6 | pages = 587–599 | date = December 2002 | pmid = 12470213 | doi = 10.2174/1389203023380404 | url = http://www.benthamdirect.org/pages/content.php?CPPS/2002/00000003/00000006/0002K.SGM | url-status = dead | archive-url = https://archive.today/20130414102134/http://www.benthamdirect.org/pages/content.php?CPPS/2002/00000003/00000006/0002K.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite book | vauthors = Robl JA, Trippodo Petrillo EW | chapter = Neutral Endopeptidase Inhibitors and Combined Inhibitors Neutral Endopeptidase and Angiotensin-Converting Enzyme | veditors = van Zwieten PA, Greenlee WJ | title = Antihypertensive Drugs | chapter-url = https://books.google.com/books?id=f8OO3B7eD6wC&pg=PA192 | access-date = 25 November 2011 | date = 5 September 1997 | publisher = CRC Press | isbn = 978-90-5702-122-0 | page = 192}} In mice, with the intracerebroventricular co-administration of a 50 μg dose of kelatorphan (this route is necessary because kelatorphan is incapable of crossing the blood-brain-barrier){{cite journal | vauthors = Boudinot E, Morin-Surun M, Foutz AS, Fournié-Zaluski M, Roques BP, Denavit-Saubié M | title = Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on respiration | journal = Pain | volume = 90 | issue = 1–2 | pages = 7–13 | date = February 2001 | pmid = 11166965 | doi = 10.1016/S0304-3959(00)00382-1 | s2cid = 26011241 }} hence alongside exogenous [Met]enkephalin (ED50 approximately 10 ng), it potentiated the analgesic effects of the latter by 50,000 times. Kelatorphan also displays potent antinociceptive effects alone,{{cite journal | vauthors = Kayser V, Fournie-Zaluski MC, Guilbaud G, Roques BP | title = Potent antinociceptive effects of kelatorphan (a highly efficient inhibitor of multiple enkephalin-degrading enzymes) systemically administered in normal and arthritic rats | journal = Brain Research | volume = 497 | issue = 1 | pages = 94–101 | date = September 1989 | pmid = 2790459 | doi = 10.1016/0006-8993(89)90974-8 | s2cid = 46293877 }} and does not depress respiration, although at high doses it actually increases it.