The non-peptide neurokinin1 receptor antagonist, RP 67580, blocks neurogenic plasma extravasation in the dura mater of rats

Br J Pharmacol. 1993 Jan;108(1):11-2. doi: 10.1111/j.1476-5381.1993.tb13432.x.

Abstract

A non-peptide neurokinin1 (NK1) receptor antagonist, RP 67580, that is selective for the rodent subtype of the NK1 receptor, dose-dependently reduced plasma extravasation in the dura mater produced by electrical stimulation of the trigeminal ganglion in rats, with an ID50 of 0.6 micrograms kg-1. Its enantiomer RP 68651 was some 400 fold less active. The results indicate that neurogenic plasma extravasation within the dura mater is NK1 receptor-mediated and suggest that NK1 receptor antagonists may have a role as antimigraine agents.

MeSH terms

  • Animals
  • Capillary Permeability / drug effects*
  • Dura Mater / blood supply*
  • Electric Stimulation
  • Indoles / pharmacology*
  • Isoindoles
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter / antagonists & inhibitors
  • Receptors, Neurotransmitter / physiology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substance P / antagonists & inhibitors*
  • Trigeminal Ganglion / physiology

Substances

  • Indoles
  • Isoindoles
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Substance P