Measurement of activity of 5-HT antagonists following oral administration in man: a comparison of methysergide and BW501.
1 Oral doses of BW501 and methysergide administered to healthy volunteers inhibited the ex vivo platelet aggregation response to 5-hydroxytryptamine (5-HT). 2 Two volunteers received 100 mg BW501 and two received 10 mg BW501 and aggregation response was measured immediately pre drug and at 1,3 and 24 h post drug. After 100 mg BW501 the response to 5-HT was completely inhibited at all times studied, after 10 BW501 a response too small to measure was apparent at 24 h only. 3 In two randomised crossover studies subjects received either 2 mg BW501 (nine subjects), 2 mg methysergide (six subjects) or no drug (nine subjects) and aggregation response to 5-HT was measured immediately pre drug and at 1, 2, 3, 5, 7, 24 h post drug. 4 Methysergide (2 mg) produced complete inhibition of aggregation for 24 h after dosing; following 2 mg BW501 the aggregation response was significantly lower than on the control occasion at 1 (P less than 0.01), 2 (P less than 0.01) and 3 (P less than 0.05) h post drug. The response was inhibited by rr%, 31% and 16% at these times respectively. 5 It is suggested that this technique provides a suitable method for demonstration of activity of 5-HT antagonists after oral dosing in man.
D000284:Administration, Oral; D000328:Adult; D000578:Amidines / Q000494:pharmacology*; D000814:Aniline Compounds / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008784:Methysergide / Q000494:pharmacology*; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D012702:Serotonin Antagonists
D000578:Amidines; D000814:Aniline Compounds; D012702:Serotonin Antagonists; D008784:Methysergide