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Chemical Compound Review

LANEPITANT     N-[(2R)-1-[ethanoyl-[(2...

Synonyms: CHEMBL42407, SureCN121512, CHEBI:164112, LS-44577, AC1MJ6LZ, ...
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Disease relevance of LY303870

  • Systemic administration of LY303870 also reversed hindpaw edema and cutaneous warmth [1].
  • Intrathecal, but not systemic administration of LY303870 reversed soft tissue and articular mechanical hyperalgesia in the hindpaw [1].
  • Postulating that facilitated substance P signaling may also contribute to the vascular and nociceptive abnormalities observed after tibial fracture or cast immobilization, we attempted to reverse these changes with LY303870 [2].
  • Previously we observed that the substance P receptor (NK(1)) antagonist LY303870 reversed vascular and nociceptive changes in a sciatic section rat model of CRPS type II [2].
  • 2 The initial hypotension (-18+/-2.0 mmHg at 1 min) and the tachycardia (110+/-10 b.p.m.) produced by the intrathecal (i.t.) injection of the stable NK(1) receptor agonist [Sar(9), Met(O(2))(11)]-SP (Sar9, 0.65 nmol) at T-9 spinal cord level was inhibited by the prior injection of 65 nmol LY306740 or LY303870 (NK(1) receptor antagonists) [3].

High impact information on LY303870

  • On the other hand, the paclitaxel-induced pulmonary vascular hyperpermeability was reversed by sensory denervation with capsaicin or pretreatment with LY303870 and SR48968, NK1 and NK2 antagonists, respectively [4].
  • Hindpaw warmth, spontaneous extravasation, edema, and allodynia were inhibited by LY303870 [2].
  • SP and SP(6-11) responses were blocked by NK-1 antagonists SR140333 and LY303870 [5].
  • Compound (R)-32, designated LY303870, is currently under clinical development as an NK-1 antagonist with a long duration of action [6].
  • Unlabeled LY303870 potently inhibited the binding with an IC50 of 0.56 nM, whereas the less active (S)-enantiomer (LY306155) was substantially less potent [7].

Chemical compound and disease context of LY303870


Biological context of LY303870

  • Consistent with the antagonist properties of LY303870, the dissociation rate of [3H]-LY303870 was not changed by the presence of 100 microM Gpp(NH)p. The distribution of [3H]LY303870 binding sites in the guinea pig brain closely matched the distribution of NK-1 receptors labeled by [3H]SP [7].
  • In vivo, LY303870 inhibited [Sar9,Met(O2)11]-SP induced guinea pig bronchoconstriction (ED50 = 75 micrograms/kg i.v.) and pulmonary microvascular leakage in the bronchi (ED50 = 12.8 micrograms/kg i.v.) and trachea (ED50 = 18.5 micrograms/kg i.v.). Therefore, LY303870 is a potent and selective NK-1 receptor antagonist in vitro and in vivo [9].
  • LY303870 and LY306740 were devoid of direct effects while LY303241 decreased blood pressure and heart rate for 1 and 10 min, respectively [8].

Anatomical context of LY303870


Associations of LY303870 with other chemical compounds

  • Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage [13].

Gene context of LY303870

  • In addition, LY303870 inhibited SP-induced rabbit vena cava contractions (pA2 = 9.4) with high (50,000-fold) selectivity vs. NK-2 or NK-3 receptor-mediated responses [9].
  • LY303870 and LY306740 appear to be the most interesting antagonists since they act in a specific and selective manner at the tachykinin NK1 receptor [8].


  1. A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II. Kingery, W.S., Davies, M.F., Clark, J.D. Pain (2003) [Pubmed]
  2. Substance P signaling contributes to the vascular and nociceptive abnormalities observed in a tibial fracture rat model of complex regional pain syndrome type I. Guo, T.Z., Offley, S.C., Boyd, E.A., Jacobs, C.R., Kingery, W.S. Pain (2004) [Pubmed]
  3. Evidence for a GABA(B) receptor component in the spinal action of Substance P (SP) on arterial blood pressure in the awake rat. Brouillette, J., Couture, R. Br. J. Pharmacol. (2002) [Pubmed]
  4. Role of sensory nerve peptides rather than mast cell histamine in paclitaxel hypersensitivity. Itoh, Y., Sendo, T., Hirakawa, T., Goromaru, T., Takasaki, S., Yahata, H., Nakano, H., Oishi, R. Am. J. Respir. Crit. Care Med. (2004) [Pubmed]
  5. Endogenous peptidergic modulation of perisynaptic Schwann cells at the frog neuromuscular junction. Bourque, M.J., Robitaille, R. J. Physiol. (Lond.) (1998) [Pubmed]
  6. 3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor antagonists. Hipskind, P.A., Howbert, J.J., Bruns, R.F., Cho, S.S., Crowell, T.A., Foreman, M.M., Gehlert, D.R., Iyengar, S., Johnson, K.W., Krushinski, J.H., Li, D.L., Lobb, K.L., Mason, N.R., Muehl, B.S., Nixon, J.A., Phebus, L.A., Regoli, D., Simmons, R.M., Threlkeld, P.G., Waters, D.C., Gitter, B.D. J. Med. Chem. (1996) [Pubmed]
  7. [3H]LY303870, a novel nonpeptide radioligand for the NK-1 receptor. Gehlert, D.R., Schober, D.A., Hipskind, P.A., Gitter, B.D., Howbert, J.J. J. Neurochem. (1996) [Pubmed]
  8. Peripheral effects of three novel non-peptide tachykinin NK1 receptor antagonists in the anaesthetized rat. Cellier, E., Fayolle, C., Hipskind, P.A., Iyengar, S., Couture, R. Eur. J. Pharmacol. (1996) [Pubmed]
  9. Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist. Gitter, B.D., Bruns, R.F., Howbert, J.J., Waters, D.C., Threlkeld, P.G., Cox, L.M., Nixon, J.A., Lobb, K.L., Mason, N.R., Stengel, P.W. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  10. The nonpeptide NK-1 receptor antagonists LY303870 and LY306740 block the responses of spinal dorsal horn neurons to substance P and to peripheral noxious stimuli. Radhakrishnan, V., Iyengar, S., Henry, J.L. Neuroscience (1998) [Pubmed]
  11. Saturable transport of the neurokinin-1 non-peptide antagonist LY303870 across the rat blood-brain barrier after intravenous administration. Banks, W.A., McMillian, C.L., Iyengar, S. Life Sci. (2001) [Pubmed]
  12. The non-peptide NK-1 receptor antagonist LY303870 inhibits neurogenic dural inflammation in guinea pigs. Phebus, L.A., Johnson, K.W., Stengel, P.W., Lobb, K.L., Nixon, J.A., Hipskind, P.A. Life Sci. (1997) [Pubmed]
  13. Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats. Hayashi, K., Sato, H., Kaise, T., Ohmori, K., Ishii, A., Sano, J., Karasawa, A. Eur. J. Pharmacol. (2001) [Pubmed]
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