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At Organon, my primary task was to predict from preclinical experiments if mianserin, a 5-HT antagonist like methysergide, would be effective in migraine. I decided therefore to investigate effects of these compounds as well as of ketanserin and cyproheptadine, on vasoconstriction elicited by 5-HT in the canine carotid vascular bed. Surprisingly, none of them attenuated 5-HT-induced vasoconstriction; methysergide even mimicked the action of 5-HT via what I called 'Atypical' 5-HT receptors. Ergotamine was found to elicited a very selective carotid vasoconstrictor action (Harold G Wolff Prize). My conclusion at Organon was that mianserin would not be effective in migraine, and one should in fact look for agonists at this 'Atypical' 5-HT (later named 5-HT1B) receptor for antimigraine efficacy. Organon did not take this suggestion and, in the mean time, I moved to Rotterdam.
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