Craniovascular selectivity of eletriptan and sumatriptan in human isolatedblood vessels

Background: Eletriptan is a 5-MT1B/1D receptor agonist with proven efficacy in the acute treatment of migraine. Objective: To assess the craniovascula r selectivity of eletriptan and sumatriptan in blood vessels predictive of therapeutic efficacy (human middle meningeal artery) and adverse coronary s ide effects (human coronary artery and human saphenous vein). Method; The a uthors obtained coronary artery from organ donors (n = 9), middle meningeal artery from patients (n = 11) undergoing craniotomy, and saphenous vein fr om patients (n = 9) undergoing coronary bypass surgery. Concentration-respo nse curves to eletriptan and sumatriptan were constructed to obtain measure ments of efficacy (maximum contraction, E-max) and potency (concentration e liciting 50% of E-max, EC50). The contraction that is likely to be induced at the maximal free plasma concentration (C-max) was determined by calculat ing C-max/EC50 ratios and by interpolation of the concentration-response cu rves. Results: Eletriptan and sumatriptan induced concentration-dependent c ontractions of meningeal artery, coronary artery, and saphenous vein. Eletr iptan was less potent than sumatriptan in coronary artery, whereas both com pounds had similar potency in meningeal artery and saphenous vein. However, the potency of eletriptan and sumatriptan was higher in meningeal artery t han in coronary artery (86-fold for eletriptan and 30-fold for sumatriptan) or saphenous vein (66- and 25-fold). The efficacy of eletriptan and sumatr iptan was similar within tissues. The predicted contraction by eletriptan ( 40 mg and 80 mg) and sumatriptan (100 mg) at free C-max observed in clinica l trials was similar in meningeal artery, whereas in coronary artery and sa phenous vein it was lower for 40 mg eletriptan than for sumatriptan. Conclu sions: At therapeutic concentrations both eletriptan and sumatriptan contra ct middle meningeal artery more than coronary artery. This suggests that in patients with healthy coronary arteries, they have a limited propensity to cause adverse coronary side effects. However, both drugs remain contraindi cated in patients with coronary artery disease.