Effect of a 5-HT1 receptor agonist, CP-122,288, on oedema formation induced by stimulation of the rat saphenous nerve.
Neurogenic oedema formation in the rat hind paw skin induced by electrical stimulation of the saphenous nerve and measured by extravasation of [125I]-albumin, was inhibited by the 5-HT1B receptor agonist, CP-93,129, and the novel tryptamine analogue, CP-122,288. Significant inhibition of up to 66% of control was observed with CP-122,288 (2 x 10(-14) - 2 x 10(-7) mol kg-1) and CP-93,129 (5 x 10(-7) - 5 x 10(-6) mol kg-1), with the minimum effective dose for CP-122,288 being about 10(7) fold less than that for CP-93,129. Oedema formation induced by the intradermal administration of exogenous mediators (substance P and histamine) in rat dorsal skin was not inhibited by CP-122,288 (2 x 10(-10) mol kg-1). These results suggest that CP-122,288 is a potent inhibitor of neurogenic inflammation in rat skin and that the effect may be due to a prejunctional inhibition of neuropeptide release.
Kajekar
R
R
Pharmacology Group, King's College, London.
Gupta
P
P
Shepperson
N B
NB
Brain
S D
SD
D000704:Analysis of Variance; D000818:Animals; D004487:Edema / Q000517:prevention & control*; D004558:Electric Stimulation; D008297:Male; D009443:Neuritis / Q000517:prevention & control; D009475:Neurons, Afferent / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000031:analogs & derivatives* / Q000494:pharmacology
D011725:Pyridines; D011758:Pyrroles; D011759:Pyrrolidines; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C085263:CP 122288; D018170:Sumatriptan