No effect of the 5HT2-antagonist ICI 169,369 on systolic, ergotamine-induced blood pressure changes in man.
The 5HT-antagonistic effect of drugs in man is difficult to study because of side effects to 5HT. Ergotamine, however contracts human arteries, probably by acting on 5HT receptors. This effect can be antagonized in vitro by the 5HT antagonist ICI 169,369. After an initial ergotamine challenge to select responders to ergotamine, 10 selected volunteers were given in a double blind study an oral dose of either placebo, 30 mg or 120 mg of ICI 169,369. After 2 hr an intravenous dose of 0.5 mg ergotamine tartrate was given. From 6 to 8 hr after the administration, ergotamine caused a mean decrease in the toe-arm systolic gradient, measured by strain-gauge plethysmography of 32 mmHg (P < 0.001), which was not influenced by either 30 mg or 120 mg ICI 169,369 (P < 0.4). The most likely explanation for our inability to detect any effect of ICI 169,369 on blood pressure changes, induced by ergotamine may be high binding (99%) of ICI 169,369 to plasma proteins. There was, however, indication of a per se vasodilatory effect of ICI 169,369 since the dose of 120 mg increased the toe-arm systolic gradient by 4.7 mmHg.
Nielsen
T H
TH
Department of Neurology, University Hospital Gentofte, Denmark.
Tfelt-Hansen
P
P
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004878:Ergotamine / Q000037:antagonists & inhibitors; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010991:Plethysmography; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013599:Systole
D011804:Quinolines; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D004878:Ergotamine