Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches.
OBJECTIVE
Second-generation triptans are believed to have fewer cardiovascular effects than sumatriptan. This was investigated in vivo by comparing the vascular effects of equipotent therapeutic dosages of selective 5-HT1B/1D-receptor agonists.


METHODS
Sixteen patients with migraine headaches completed a double-blind, placebo-controlled, four-way crossover study. With ultrasonography and applanation tonometry used 1.5 hours after the oral intake of sumatriptan (50 mg), rizatriptan (10 mg), zolmitriptan (2.5 mg), or placebo arterial vessel wall properties, blood flow and pressure waveforms were measured in common carotid, brachial, and temporal arteries. At the brachial artery, flow-induced vasodilation (an endothelium-dependent process) was evaluated, and blood pressures were recorded.


RESULTS
Mean arterial pressure, 91 +/- 2 mm Hg after placebo, increased (P < .05) by 4% to 6% after administration of each triptan. Each active treatment decreased (P < .001) both brachial and carotid artery diameter. Isobaric compliance of the brachial artery, 0.077 +/- 0.010 mm2/kPa after placebo, decreased (P < .01) by 11% +/- 8%, 11% +/- 11%, and 23% +/- 7% after administration of sumatriptan, rizatriptan, and zolmitriptan, respectively. Isobaric compliance of the carotid artery was 1.31 +/- 0.10 mm2/kPa after placebo (no change). Zolmitriptan was the only triptan that decreased temporal artery diameter significantly (by 12% +/- 3%, P < .001). The resistance of the temporal artery vascular bed increased after administration of sumatriptan (by 26% +/- 11%, P < .05) and zolmitriptan (by 40% +/- 9%, P = .001). Flow-induced vasodilation was unaffected.


CONCLUSIONS
Selective 5-HT1B/1D-receptor agonists induce vasoconstriction and decrease compliance of conduit arteries. These effects are more pronounced at muscular (temporal, brachial) compared with elastic (carotid) arteries. Resistance is only increased at the temporal artery vascular bed, suggesting cranioselectivity for resistance vessels. Endothelial function is not differently affected by any of the triptans tested.
de Hoon
J N
JN
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, The Netherlands.
Willigers
J M
JM
Troost
J
J
Struijker-Boudier
H A
HA
Van Bortel
L M
LM
D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D023303:Oxazolidinones / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D013699:Temporal Arteries / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*; D014363:Tryptamines; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C089750:zolmitriptan; C093622:rizatriptan; D018170:Sumatriptan