The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT 1C receptor agonists in piglet choroid plexus

1 Fozard & Gray (1989) proposed that migraine is mediated by stimulation of 5‐HT 1C receptors. We have examined the interaction of two effective anti‐migraine agents, ergotamine and dihydroergotamine (DHE), with these receptors. Binding (inhibition of labelling by [ 3 H]‐mesulergine) and agonist activity (phosphoinositide hydrolysis) were measured in piglet choroid plexus, a tissue rich in 5‐HT 1C receptors. 2 The p K D for [ 3 H]‐mesulergine binding was 8.4. Ergotamine and DHE both inhibited [ 3 H]‐mesulergine binding with a p K D of 7.1. This was similar to the potency of m ‐chlorophenylpiperazine ( m ‐CPP) (p K D 7.4) and rather less than that of 5‐hydroxytryptamine (5‐HT) (p K D 8.1). 3 Both ergotamine and DHE were full agonists (pEC 50 s 7.5 and 7.6 respectively) with potencies similar to that of 5‐HT (pEC 50 7.7) and greater than that of m ‐CPP (pEC 50 7.1). Mesulergine 10 −7 m produced near‐parallel rightward shifts of the concentration‐response curves for all these agents of 1.8–2.2 log units, consistent with an action of the agonists at the same receptor. 4 There was no effect of prazosin, spiperone, mepyramine or atropine on the phosphoinositide hydrolysis induced by ergotamine, ruling out an action via α 1 ‐adrenoceptors, 5‐HT 2 , histamine H 1 , or muscarinic receptors. 5 It is concluded that, together with 5‐HT, ergotamine and DHE are the most potent 5‐HT 1C agonists reported so far. These findings do not support the theory that 5‐HT 1C receptor activation causes migraine.