Premium
Blockade by oral or parenteral RPR 100893 (a non‐peptide NK 1 receptor antagonist) of neurogenic plasma protein extravasation within guinea‐pig dura mater and conjunctiva
Author(s) -
Lee Won S.,
Moussaoui Saliha M.,
Moskowitz Michael A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13168.x
Subject(s) - extravasation , trigeminal ganglion , stimulation , dura mater , neurogenic inflammation , nk1 receptor antagonist , chemistry , evans blue , endocrinology , guinea pig , medicine , capsaicin , antagonist , receptor , pharmacology , substance p , pathology , anatomy , biology , neuropeptide , sensory system , neuroscience
1 The ability of an NK 1 receptor antagonist, RPR 100893, and its enantiomer, RPR 103253 to block neurogenic plasma protein extravasation in guinea‐pig dura mater and conjunctiva was assessed following 125 I‐labelled bovine serum albumin ([ 125 I]‐BSA, 50 μCi kg −1 , i.v.) and unilateral electrical stimulation of the trigeminal ganglion (0.6 mA, 5 ms, 5 Hz, 5 min) or capsaicin administration (150 μg kg −1 , i.v.). 2 When administered p.o. 60 min prior to electrical stimulation, RPR 100893 (≥ 0.1 μg kg −1 ) decreased plasma protein extravasation in dura mater in a dose‐dependent manner, whereas the enantiomer (10 or 100 μg kg −1 , p.o.) was inactive. 3 When given i.v. 30 min prior to electrical stimulation, RPR 100893 (≥ 0.5 ng kg −1 ) significantly inhibited plasma protein extravasation in the dura mater evoked by electrical stimulation in a dose‐dependent manner. 4 RPR 100893 (100 μg kg −1 , p.o.) also reduced the leakage when given 45 min before the guinea‐pigs were killed and 10, 40 and 80 min after electrical trigeminal stimulation. 5 RPR 100893 given p.o. dose‐dependently inhibited capsaicin‐induced plasma protein extravasation with ID 50 s of 7.4 μg kg −1 and 82 μg kg −1 for dura mater and conjunctiva, respectively. 6 These results are consistent with the contention that NK 1 receptors mediate neurogenic plasma protein leakage following trigeminal stimulation, and suggest that NK 1 receptor antagonists of the perhydroisoindolone series may be useful for treating migraine and cluster headaches.