for the treatment of a severe intractable migraine. Another ergot derivative, methysergide
(4.123), is a safer compound for chronic prophylactic use. The interactions of ergots
with serotonin receptors is complex, since these agents can be agonists, antagonists, or
partial agonists at one or more of the various serotonin receptors. Ergotamine and
methysergide are serotonin antagonists as well as partial agonists effective at 5-HT 2
receptors.
4.6 HISTAMINE AND THE HISTAMINE RECEPTORS
The role of histamine as a central neurotransmitter has long been recognized, and a con-
siderable amount of research has been directed toward elucidating its central effects and
receptors. The additional discovery of the duality of the histamine receptor (i.e., both
inside and outside the brain) has added another dimension to this complex field, leading
to new and successful therapeutic as well as theoretical investigations.
260 MEDICINAL CHEMISTRY