Kelatorphan

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).^[1][2][3] 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)^[4] hence alongside exogenous [Met]enkephalin (ED₅₀ approximately 10 ng), it potentiated the analgesic effects of the latter by 50,000 times.^[1] Kelatorphan also displays potent antinociceptive effects alone,^[5] and does not depress respiration, although at high doses it actually increases it.^[4]

Kelatorphan

Clinical data
ATC code	None
Legal status
Legal status	In general: non-regulated
Identifiers
IUPAC name N-[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-L-alanine
CAS Number	92175-57-0
PubChem CID	123982
DrugBank	DB08040
ChemSpider	110501
UNII	46BBW2U5D6
CompTox Dashboard (EPA)	DTXSID90238911
Chemical and physical data
Formula	C14H18N2O5
Molar mass	294.307 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)[C@@H](NC(=O)[C@H](Cc1ccccc1)CC(=O)NO)C
InChI InChI=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 Key:OJCFZTVYDSKXNM-GXSJLCMTSA-N

See also

• Enkephalinase inhibitor

References

1. Fournie-Zaluski MC, Chaillet P, Bouboutou R, Coulaud A, Cherot P, Waksman G, et al. (July 1984). "Analgesic effects of kelatorphan, a new highly potent inhibitor of multiple enkephalin degrading enzymes". European Journal of Pharmacology. 102 (3–4): 525–528. doi:10.1016/0014-2999(84)90575-2. PMID 6386492.
2. Yamamoto Y, Ono H, Ueda A, Shimamura M, Nishimura K, Hazato T (December 2002). "Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation". Current Protein & Peptide Science. 3 (6): 587–599. doi:10.2174/1389203023380404. PMID 12470213. Archived from the original on 2013-04-14.
3. Robl JA, Trippodo Petrillo EW (5 September 1997). "Neutral Endopeptidase Inhibitors and Combined Inhibitors Neutral Endopeptidase and Angiotensin-Converting Enzyme". In van Zwieten PA, Greenlee WJ (eds.). Antihypertensive Drugs. CRC Press. p. 192. ISBN 978-90-5702-122-0. Retrieved 25 November 2011.
4. Boudinot E, Morin-Surun M, Foutz AS, Fournié-Zaluski M, Roques BP, Denavit-Saubié M (February 2001). "Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on respiration". Pain. 90 (1–2): 7–13. doi:10.1016/S0304-3959(00)00382-1. PMID 11166965. S2CID 26011241.
5. Kayser V, Fournie-Zaluski MC, Guilbaud G, Roques BP (September 1989). "Potent antinociceptive effects of kelatorphan (a highly efficient inhibitor of multiple enkephalin-degrading enzymes) systemically administered in normal and arthritic rats". Brain Research. 497 (1): 94–101. doi:10.1016/0006-8993(89)90974-8. PMID 2790459. S2CID 46293877.