ENDOTHELIN ANTAGONIST BOSENTAN BLOCKS NEUROGENIC INFLAMMATION, BUT ISNOT EFFECTIVE IN ABORTING MIGRAINE ATTACKS

Bosentan, a specific mixed antagonist of endothelin receptors with no vasoconstrictor activity, inhibits neurogenic plasma extravasation (NP E) within rat dura mater. This would predict efficacy in aborting migr aine attacks, without causing cardiovascular side-effects, We investig ated the efficacy of 250 mg i.v, bosentan in a randomized, double-blin d, placebo-controlled, clinical trial. Improvement from moderate/sever e to mild/no headache at 2 h (primary efficacy measure) occurred in 5/ 23 (22%) of bosentan-treated and in 9/25 (36%) of placebo-treated pati ents (effect difference -14%; 95% CI -52%, 24%). Thus, inhibition of N PE may not predict clinical efficacy of experimental antimigraine drug s. Vasoconstrictor action may be needed.