Comparison of the vasoconstrictor properties of the 5-HT1D-receptor agonists rizatriptan (MK-462) and sumatriptan in human isolated coronary artery: outcome of two independent studies using different experimental protocols.
Rizatriptan (MK-462) is a novel 5-HT1D-receptor agonist and is effective in the treatment of migraine headache. As angiographic studies have shown that the prototypic 5-HT1D/1B-receptor agonist sumatriptan can cause coronary artery constriction in patients with mild coronary artery disease, we have compared the contractile effects of rizatriptan on human isolated coronary artery with those of sumatriptan and 5-HT. Two different experimental protocols were used. In Study 1 (to avoid agonist desensitisation and interaction effects), arterial segments were exposed to a single agonist (either 5-HT, sumatriptan or rizatriptan) and in Study 2 each arterial segment was exposed to all three agonists with randomised first exposure to sumatriptan or rizatriptan. In both these studies the maximum contractions evoked by sumatriptan and rizatriptan were found to be smaller than those evoked by 5-HT, and the maximum contraction evoked by rizatriptan was significantly smaller than that for sumatriptan.
Longmore
J
J
Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK.
Hargreaves
R J
RJ
Boulanger
C M
CM
Brown
M J
MJ
Desta
B
B
Ferro
A
A
Schofield
W N
WN
Taylor
A A
AA
Hill
R G
RG
D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D014363:Tryptamines; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; D014662:Vasoconstrictor Agents; D012701:Serotonin; C093622:rizatriptan; D018170:Sumatriptan