Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels.
BACKGROUND
Eletriptan is a 5-HT(1B/1D) receptor agonist with proven efficacy in the acute treatment of migraine.


OBJECTIVE
To assess the craniovascular selectivity of eletriptan and sumatriptan in blood vessels predictive of therapeutic efficacy (human middle meningeal artery) and adverse coronary side effects (human coronary artery and human saphenous vein).


METHODS
The authors obtained coronary artery from organ donors (n = 9), middle meningeal artery from patients (n = 11) undergoing craniotomy, and saphenous vein from patients (n = 9) undergoing coronary bypass surgery. Concentration-response curves to eletriptan and sumatriptan were constructed to obtain measurements of efficacy (maximum contraction, E(max)) and potency (concentration eliciting 50% of E(max), EC(50)). The contraction that is likely to be induced at the maximal free plasma concentration (C(max)) was determined by calculating C(max)/EC(50) ratios and by interpolation of the concentration-response curves.


RESULTS
Eletriptan and sumatriptan induced concentration-dependent contractions of meningeal artery, coronary artery, and saphenous vein. Eletriptan was less potent than sumatriptan in coronary artery, whereas both compounds had similar potency in meningeal artery and saphenous vein. However, the potency of eletriptan and sumatriptan was higher in meningeal artery than in coronary artery (86-fold for eletriptan and 30-fold for sumatriptan) or saphenous vein (66- and 25-fold). The efficacy of eletriptan and sumatriptan was similar within tissues. The predicted contraction by eletriptan (40 mg and 80 mg) and sumatriptan (100 mg) at free C(max) observed in clinical trials was similar in meningeal artery, whereas in coronary artery and saphenous vein it was lower for 40 mg eletriptan than for sumatriptan.


CONCLUSIONS
At therapeutic concentrations both eletriptan and sumatriptan contract 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 contraindicated in patients with coronary artery disease.
MaassenVanDenBrink
A
A
Department of Pharmacology, Erasmus University Medical Centre Rotterdam "EMCR," the Netherlands. maassenvandenbrink@farma.fgg.eur.nl
van den Broek
R W
RW
de Vries
R
R
Bogers
A J
AJ
Avezaat
C J
CJ
Saxena
P R
PR
D000368:Aged; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014363:Tryptamines
D007211:Indoles; D011759:Pyrrolidines; D014363:Tryptamines; C115647:eletriptan; D018170:Sumatriptan