Enantioselective inhibition of the formalin paw late phase by the NK1 receptor antagonist L-733,060 in gerbils

Pain. 1996 Sep;67(1):189-95. doi: 10.1016/0304-3959(96)03109-0.

Abstract

Intravenous administration of the NK1 receptor antagonist L-733,060 to gerbils 3 h before intraplantar injection of formalin caused a dose-dependent and complete inhibition of the late, but not early, phase nociceptive response (paw licking). The ID50 for L-733,060 (0.17 mg/kg) revealed a greater than 50-fold separation in potency over its less active enantiomer L-733,061 (ID50 > or = 10 mg/kg). In contrast, the non-brain penetrant quaternary ketone NK1 receptor antagonist, L-743,310 (3 mg/kg), did not attenuate the response to formalin, indicating that the antinociceptive effect of blockade of NK1 receptors by L-733,060 in this assay is centrally-mediated. These findings add to the preclinical evidence that NK1 receptor antagonists may be of therapeutic use as centrally-acting analgesics.

MeSH terms

  • Animals
  • Female
  • Foot
  • Formaldehyde / pharmacology*
  • Gerbillinae
  • Injections
  • Male
  • Motor Activity / drug effects
  • Neurokinin-1 Receptor Antagonists*
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Stereoisomerism
  • Substance P / analogs & derivatives
  • Substance P / antagonists & inhibitors
  • Substance P / pharmacology
  • Time Factors

Substances

  • Neurokinin-1 Receptor Antagonists
  • Peptide Fragments
  • Piperidines
  • GR 73632
  • 3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
  • Formaldehyde
  • Substance P