Inhibition of neurogenic inflammation in the meninges by a non-peptide NK1 receptor antagonist, RP 67580.
RP 67580, a non-peptide NK1 receptor antagonist, inhibited in a stereoselective and dose-dependent manner plasma extravasation caused in the dura mater by intravenous injection of capsaicin in guinea-pigs and of exogenous substance P in rats (ED50 = 35 and 2.5 micrograms/kg i.v., respectively). In the two species, RP 67580 appeared to be more effective in the dura mater than in the peripheral organs. These results indicate that selective NK1 receptor antagonists could be potentially effective for the treatment of migraine headache.
Moussaoui
S M
SM
Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry, Alfortville, Vitry sur Sein, France.
Philippe
L
L
Le Prado
N
N
Garret
C
C
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000187:drug effects*; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D008578:Meninges / Q000187:drug effects*; D008881:Migraine Disorders / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D007211:Indoles; D054833:Isoindoles; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D002211:Capsaicin