Kelatorphan Explained

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. Kelatorphan also displays potent antinociceptive effects alone,^[5] and does not depress respiration, although at high doses it actually increases it.^[4]

See also

• Enkephalinase inhibitor

Notes and References

1. Fournie-Zaluski MC, Chaillet P, Bouboutou R, Coulaud A, Cherot P, Waksman G, Costentin J, Roques BP . 6 . Analgesic effects of kelatorphan, a new highly potent inhibitor of multiple enkephalin degrading enzymes . European Journal of Pharmacology . 102 . 3–4 . 525–528 . July 1984 . 6386492 . 10.1016/0014-2999(84)90575-2 .
2. Yamamoto Y, Ono H, Ueda A, Shimamura M, Nishimura K, Hazato T . Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation . Current Protein & Peptide Science . 3 . 6 . 587–599 . December 2002 . 12470213 . 10.2174/1389203023380404 . dead . https://archive.today/20130414102134/http://www.benthamdirect.org/pages/content.php?CPPS/2002/00000003/00000006/0002K.SGM . 2013-04-14 .
3. Book: Robl JA, Trippodo Petrillo EW . Neutral Endopeptidase Inhibitors and Combined Inhibitors Neutral Endopeptidase and Angiotensin-Converting Enzyme . van Zwieten PA, Greenlee WJ . Antihypertensive Drugs . https://books.google.com/books?id=f8OO3B7eD6wC&pg=PA192 . 25 November 2011 . 5 September 1997 . CRC Press . 978-90-5702-122-0 . 192.
4. Boudinot E, Morin-Surun M, Foutz AS, Fournié-Zaluski M, Roques BP, Denavit-Saubié M . Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on respiration . Pain . 90 . 1–2 . 7–13 . February 2001 . 11166965 . 10.1016/S0304-3959(00)00382-1 . 26011241 .
5. Kayser V, Fournie-Zaluski MC, Guilbaud G, Roques BP . 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 . September 1989 . 2790459 . 10.1016/0006-8993(89)90974-8 . 46293877 .