(especially those who both smoke and are receiving the birth control pill), migraine can
be a risk factor for stroke.
Since migraine is so common and so painful, numerous therapies have been put
forth over the years. The simplest therapies are the analgesics such as acetaminophen,
acetylsalicylic acid, or codeine. Such analgesics are acceptable if the headaches are
infrequent. However, daily use of such analgesics can, paradoxically, make the head-
aches worse in a phenomenon referred to as analgesic rebound headaches. For people
who experience several migraines per week, the use of a prophylactic agent to prevent
migraine occurrence is indicated. A wide variety of drugs have enjoyed success as
migraine prophylactic agents, including β-adrenergic blockers (propranolol), tricyclic
antidepressants (amitriptyline), Na+ channel active anticonvulsants (valproic acid,
4.132), and Ca^2 +channel active agents (verapamil,4.133, diltiazem,4.134).
However, the class of agents with the greatest success against migraine has been
based on a serotonergic approach. The success of serotonergic drugs reflects the fact
that the mechanism of migraine involves a vascular (“vasomotor”) component. Current
studies on migraine have revealed the involvement of numerous serotonergic nerve
endings in blood vessels within the meninges (coverings over the brain); during a
migraine attack these cranial blood vessels become swollen and inflamed. Over the
past decade, the acute treatment of migraine has been revolutionized by the “triptans,”
including sumatriptan (4.135), naratriptan (4.136), rizatriptan (4.137), and zolmitriptan
(4.138). These compounds are selective agonists for 5-HT1Dand 5-HT1Breceptors,
which are found on blood vessels in the meninges and mediate vasoconstriction in these
vessels. In addition to the triptans, the ergot alkaloids are also effective against
migraine. The efficacy of ergot derivatives in migraine is so specific that it almost con-
stitutes a diagnostic test. Traditionally, ergotamine, when given during the aura, is par-
ticularly effective. Dihydroergotamine (4.139) is commonly employed intravenously
NEUROTRANSMITTERS AND THEIR RECEPTORS 259