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Kelatorphan

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Chemical compound

Pharmaceutical compound

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
PubChemCID	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

Kelatorphan is adrug which acts as a powerful and completeinhibitor of nearly all of theenzymes responsible forcatabolism of theendogenous enkephalins, includingneutral endopeptidase (NEP),dipeptidyl peptidase III (DPP3),aminopeptidase N (APN), andangiotensin-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 theblood-brain-barrier)^[4] hence alongsideexogenous [Met]enkephalin (ED₅₀ approximately 10 ng), it potentiated theanalgesic effects of the latter by 50,000 times.^[1] Kelatorphan also displayspotent antinociceptive effects alone,^[5] and does not depressrespiration, although at high doses it actually increases it.^[4]

References

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^^a ^bFournie-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.
^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 fromthe original on 2013-04-14.
^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. Retrieved25 November 2011.
^^a ^bBoudinot 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.
^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.