Eletriptan, a second-generation
triptan with high affinity for 5-HT(1B/1D) receptors, is highly effective in
migraine, with or without
aura. We compared the effects of
eletriptan and
sumatriptan on the human isolated middle meningeal and coronary arteries and saphenous vein, used as models for therapeutic efficacy and potential side effects, and have investigated the role of 5-HT(1B/1D) receptors in contractions induced by these
triptans. Concentration-response curves to
eletriptan and
sumatriptan were constructed in the absence or presence of a selective 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-py rid yl)
benzamide (GR125743). All three blood vessels constricted in response to
eletriptan and
sumatriptan, but the middle meningeal artery relaxed following the highest concentration (100 microM) of
eletriptan. In the middle meningeal artery, GR125743 antagonised the contractions induced by both
eletriptan (pEC(50): 7.34+/-0.13) and
sumatriptan (pEC(50): 6.91+/-0.17) to a similar degree (pA(2): 8. 81+/-0.17 and 8.64+/-0.21, respectively). In the human coronary artery and saphenous vein,
sumatriptan-induced contractions (pEC(50): 6.24+/-0.14 and 6.19+/-0.12, respectively) were also potently antagonised by GR125743 (pA(2): 8.18+/-0.27 and 8.34+/-0.12, respectively). The
eletriptan-induced contractions of the human saphenous vein (pEC(50): 6.09+/-0.13) were antagonised less effectively by GR125743 (pK(B): 7.73+/-0.18), and those of the human coronary artery (pEC(50): 5.54+/-0.22) remained unaffected by GR125743 up to a concentration of 100 nM. These results suggest that (i) based on the differences in pEC(50) values, the cranioselectivity of
eletriptan (63-fold) is higher than that of
sumatriptan (5-fold) in coronary artery, (ii) the contractile effects of
sumatriptan and
eletriptan (lower concentrations) in the three blood vessels are mediated via the
5-HT(1B) receptor, and (iii) additional mechanisms seem to be involved in coronary artery and saphenous vein contractions and middle meningeal artery relaxation following high concentrations of
eletriptan.