The non-peptide neurokinin1 receptor antagonist, RP 67580, blocks neurogenic plasma extravasation in the dura mater of rats.
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.
Shepheard
S L
SL
Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Terlings Park, Harlow, Essex.
Williamson
D J
DJ
Hill
R G
RG
Hargreaves
R J
RJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004388:Dura Mater / Q000098:blood supply*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors*; D012668:Trigeminal Ganglion / Q000502:physiology
D007211:Indoles; D054833:Isoindoles; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P