The effect of rizatriptan, ergotamine, and their combination on human peripheral arteries: a double-blind, placebo-controlled, crossover study in normal subjects.
OBJECTIVE
To compare the peripheral vasoconstrictor effects of ergotamine, rizatriptan, and their combination, in normal subjects.


METHODS
This was a double-blind, four-way, crossover study. Sixteen young male volunteers, selected as responders to the vasoconstrictor effect of 0.5 mg ergotamine i.v., were administered 10 mg oral rizatriptan, 0.25 mg i.v. ergotamine, 10 mg oral rizatriptan+0.25 mg i.v. ergotamine, and placebo. The vasoconstrictor effect on peripheral arteries was measured with strain gauge plethysmography up to 8 h after dosing. The 8 h assessment period was divided into two 4 h intervals to assess the immediate (0-4 h) vs sustained effect (4-8 h) of treatment.


RESULTS
For the 0-4 h interval, the decreases in peripheral systolic blood pressure gradients were: placebo (-1 mmHg [95% CI: -3, 1])<rizatriptan (-5 mmHg [95% CI: -7, -3])<ergotamine (-15 mmHg [95% CI: -16, -13])=rizatriptan+ergotamine (-15 mmHg [95% CI: -17, -13]). For the 4-8 h interval, the decreases were: placebo (-5 mmHg [95% CI: -8, -3])=rizatriptan (-8 mmHg [95% CI: -11, -5])<ergotamine (-26 mmHg [95% CI: -29, -24])=rizatriptan+ergotamine (-28 mmHg [95% CI: -31, -26]).


CONCLUSIONS
In normal subjects, rizatriptan 10 mg orally had only a small transient vasoconstrictor effect on peripheral arteries compared with the sustained and more pronounced effect of 0.25 mg i.v. ergotamine. Furthermore, rizatriptan exerted no additional effect on ergotamine-induced constriction of peripheral arteries when the two drugs were given in combination.
Tfelt-Hansen
Peer
P
Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. tfelt@inet.uni2.dk
Seidelin
Kaj
K
Stepanavage
Michael
M
Lines
Christopher
C
D000328:Adult; D001158:Arteries / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004878:Ergotamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014363:Tryptamines; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D004338:Drug Combinations; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C093622:rizatriptan; D004878:Ergotamine