Kelatorphan

Kelatorphan
Clinical data
ATC code
  • None
Legal status
Legal status
  • In general: non-regulated
Identifiers
  • N-[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-L-alanine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H18N2O5
Molar mass294.307 g·mol−1
3D model (JSmol)
  • O=C(O)[C@@H](NC(=O)[C@H](Cc1ccccc1)CC(=O)NO)C
  • 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

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). 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) 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, and does not depress respiration, although at high doses it actually increases it.

See also

References

  1. 1 2 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.{{cite journal}}: CS1 maint: deprecated archival service (link)
  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. 1 2 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.