The effect of rizatriptan, ergotamine, and their combination on human peripheral arteries: a double‐blind, placebo‐controlled, crossover study in normal subjects

• Published in: British journal of clinical pharmacology Vol. 54; no. 1; pp. 38 - 44
• Main Authors: Tfelt‐Hansen, Peer, Seidelin, Kaj, Stepanavage, Michael, Lines, Christopher
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2002; Blackwell Science; Blackwell Science Inc
• Subjects: Adult; Arteries - drug effects; Biological and medical sciences; Cardiovascular system; Cross-Over Studies; Double-Blind Method; Drug Combinations; ergotamine; Ergotamine - administration & dosage; Ergotamine - adverse effects; Ergotamine - pharmacology; Heart Rate - drug effects; Humans; Male; Medical sciences; migraine; Migraine Disorders - drug therapy; peripheral arteries; Pharmacodynamics; Pharmacology. Drug treatments; rizatriptan; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - adverse effects; Serotonin Receptor Agonists - pharmacology; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - pharmacology; Tryptamines; Vasoconstriction - drug effects; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - adverse effects; Vasoconstrictor Agents - pharmacology; Vasodilator agents. Cerebral vasodilators; Human; Agonist; Drug combination; Intravenous administration; Healthy subject; Antimigrainous agent; Vasoconstriction; Oral administration; Tryptamine derivatives; Ergot derivatives; Serotonine receptor; Biological activity; Ergotamine; Clinical trial; Rizatriptan; Vasoconstrictor agent; Drug interaction; Blood pressure; Indole derivatives
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2002.01403.x

Aims  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.