Lanepitant

Lanepitant (INN,[1]: 48  code name LY303870) is a drug developed by Eli Lilly which acts as a selective antagonist for the NK1 receptor, and was one of the first compounds developed that act at this target.[2] It was under development as a potential analgesic drug, but despite promising results in initial animal studies, human clinical trials against migraine, arthritis and diabetic neuropathy all failed to show sufficient efficacy to support further development, with the drug being only marginally more effective than placebo and inferior to older comparison drugs such as naproxen.[3][4][5] Failure of analgesic action was thought to be due to poor penetration of the blood–brain barrier in humans, but research has continued into potential applications in the treatment of other disorders with a peripheral site of action, such as corneal neovascularization.[6]

Lanepitant
Clinical data
Other namesLY303870; N-[(R)-2-Indol-3-yl-1-[[N-(o-methoxybenzyl)acetamido]methyl]ethyl][1,4'-bipiperidine]-1'-acetamide
ATC code
  • None
Identifiers
IUPAC name
  • N-[(2R)-1-[Acetyl-[(2-methoxyphenyl)methyl]
    amino]-3-(1H-indol-3-yl)propan-2-yl]-2-(4-piperidin-1-ylpiperidin-1-yl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC33H45N5O3
Molar mass559.755 g·mol−1
3D model (JSmol)
SMILES
  • CC(=O)N(CC1=CC=CC=C1OC)C[C@@H](CC2=CNC3=CC=CC=C32)NC(=O)CN4CCC(CC4)N5CCCCC5
InChI
  • InChI=1S/C33H45N5O3/c1-25(39)38(22-26-10-4-7-13-32(26)41-2)23-28(20-27-21-34-31-12-6-5-11-30(27)31)35-33(40)24-36-18-14-29(15-19-36)37-16-8-3-9-17-37/h4-7,10-13,21,28-29,34H,3,8-9,14-20,22-24H2,1-2H3,(H,35,40)/t28-/m1/s1
  • Key:CVXJAPZTZWLRBP-MUUNZHRXSA-N

References
  1. "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 39" (PDF). World Health Organization. 1998. Retrieved 17 November 2016.
  2. Gitter BD, Bruns RF, Howbert JJ, Waters DC, Threlkeld PG, Cox LM, et al. (November 1995). "Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist". The Journal of Pharmacology and Experimental Therapeutics. 275 (2): 737–44. PMID 7473161.
  3. Goldstein DJ, Offen WW, Klein EG, Phebus LA, Hipskind P, Johnson KW, Ryan RE (March 2001). "Lanepitant, an NK-1 antagonist, in migraine prevention". Cephalalgia. 21 (2): 102–6. doi:10.1046/j.1468-2982.2001.00161.x. PMID 11422091. S2CID 27388670.
  4. Goldstein DJ, Wang O, Todd LE, Gitter BD, DeBrota DJ, Iyengar S (April 2000). "Study of the analgesic effect of lanepitant in patients with osteoarthritis pain". Clinical Pharmacology and Therapeutics. 67 (4): 419–26. doi:10.1067/mcp.2000.105243. PMID 10801252. S2CID 31571009.
  5. Goldstein DJ, Wang O, Gitter BD, Iyengar S (2001). "Dose-response study of the analgesic effect of lanepitant in patients with painful diabetic neuropathy". Clinical Neuropharmacology. 24 (1): 16–22. doi:10.1097/00002826-200101000-00004. PMID 11290877. S2CID 46162128.
  6. Bignami F, Giacomini C, Lorusso A, Aramini A, Rama P, Ferrari G (September 2014). "NK1 receptor antagonists as a new treatment for corneal neovascularization". Investigative Ophthalmology & Visual Science. 55 (10): 6783–94. doi:10.1167/iovs.14-14553. PMID 25228541.
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