Lanepitant

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of Lanepitant
General
Non-proprietary name Lanepitant
other names
  • N - [(2 R ) -1- [acetyl - [(2-methoxyphenyl) methyl] amino] -3- (1 H -indol-3-yl) propan-2-yl] -2- (4-piperidin- 1-ylpiperidin-1-yl) acetamide
  • LY303870
Molecular formula C 33 H 45 N 5 O 3
External identifiers / databases
CAS number 170566-84-4
PubChem 3086681
ChemSpider 2343246
Wikidata Q1804824
Drug information
Mechanism of action

NK 1 - antagonist

properties
Molar mass 559.74 g · mol -1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lanepitant is a chemical compound that has been developed as a potential drug for the treatment of pain , including migraine headache. After no migraine efficacy could be observed in clinical studies , its further clinical development for this application area by the pharmaceutical company Eli Lilly and Company was discontinued. Pharmacologically Lanepitant is a neurokinin - antagonist .

Mechanism of action

As an antagonist, Lanepitant inhibits the effects of substance P mediated by the neurokinin NK 1 receptor . Experimentally, Lanepitant has anti-inflammatory properties and properties that influence pain perception. In animal experiments in which the pathophysiology of migraines was simulated, the substance inhibits the inflammatory reaction in the meninges . Animal experiments also suggested a possible effectiveness in neuropathic pain and in complex regional pain syndrome . In clinical studies , however, neither migraine nor analgesic efficacy in diabetic neuropathy and osteoarthritis could be proven.

Stereochemical structure

Lanepitan is a chiral chemical compound with a stereocenter . It is the R - enantiomer and at the same time the biologically more active stereoisomer ( eutomer ) of N - [1- [acetyl - [(2-methoxyphenyl) methyl] amino] -3- (1 H -indol-3-yl) propane-2 -yl] -2- (4-piperidin-1-yl-piperidin-1-yl) acetamide. Compared to the L enantiomer, its distomer , Lanepitant has an affinity for the neurokinin NK 1 receptor that is at least 1000 times higher .

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ a b Goldstein DJ, Offen WW, Klein EG, et al. : Lanepitant, an NK-1 antagonist, in migraine prevention . In: Cephalalgia . 21, No. 2, March 2001, pp. 102-106. PMID 11422091 .
  3. ↑ a b Goldstein DJ, Wang O, Saper JR, Stoltz R, Silberstein SD, Mathew NT: Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study . In: Cephalalgia . 17, No. 7, November 1997, pp. 785-790. PMID 9399010 .
  4. ↑ Iyengar S, Hipskind PA, Gehlert DR, et al. : LY303870, a centrally active neurokinin-1 antagonist with a long duration of action . In: J. Pharmacol. Exp. Ther. . 280, No. 2, February 1997, pp. 774-785. PMID 9023291 .
  5. ↑ Phebus LA, Johnson KW, Stengel PW, Lobb KL, Nixon JA, Hipskind PA: The non-peptide NK-1 receptor antagonist LY303870 inhibits neurogenic dural inflammation in guinea pigs . In: Life Sci . 60, No. 18, 1997, pp. 1553-1561. PMID 9126877 .
  6. ↑ Campbell EA, Gentry CT, Patel S, Panesar MS, Walpole CS, Urban L: Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of neuropathic pain in the guinea-pig . In: Neuroscience . 87, No. 3, December 1998, pp. 527-532. PMID 9758219 .
  7. ↑ Guo TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS: Substance P signaling Contributes to the vascular and nociceptive abnormalities Observed in a tibial fracture rat model of Complex Regional Pain Syndrome type I . In: Pain . 108, No. 1-2, March 2004, pp. 95-107. doi : 10.1016 / j.pain.2003.12.010 . PMID 15109512 .
  8. ↑ Kingery WS, Davies MF, Clark JD: A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II . In: Pain . 104, No. 1-2, July 2003, pp. 75-84. PMID 12855316 .
  9. ↑ Goldstein DJ, Wang O, Grid BD, Iyengar S: Dose-response study of the analgesic effect of lanepitant in patients with painful diabetic neuropathy . In: Clin Neuropharmacol . 24, No. 1, 2001, pp. 16-22. PMID 11290877 .
  10. ↑ Goldstein DJ, Wang O, Todd LE, lattice BD, DeBrota DJ, Iyengar S: Study of the analgesic effect of lanepitant in patients with osteoarthritis pain . In: Clin Pharmacol Ther . 67, No. 4, April 2000, pp. 419-426. doi : 10.1067 / mcp.2000.105243 . PMID 10801252 .
  11. ^ Lattice BD, Bruns RF, Howbert JJ, et al. : Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist . In: J. Pharmacol. Exp. Ther. . 275, No. 2, November 1995, pp. 737-744. PMID 7473161 .