Role of Oral 5-HT1 Agonists in Migraine Management

The role of 5-HT₁ agonist drugs is very important in management of migraine headache, because stimulation of 5-HT_1B/1D receptors can stop an acute migraine attack. 5-HT_1B/1D receptor agonists can be selective and non selective type. Ergotamine and dihydro-ergotamine are nonselective5-HT_1B/1D receptor agonists, while the triptans are selective 5-HT_1B/1D receptor agonists. Sumatriptan, naratriptan, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan etc. are commonly known as triptans and they are commonly used in treatment of migraine.

The drugs of triptan class have similar pharmacologic properties but may vary slightly in terms of clinical efficacy (effectiveness in treatment). Rizatriptan and eletriptan are the most efficacious of the triptans, which are currently available. Sumatriptan and zolmitriptan have similar rates of efficacy as well as time to onset and they are moderately efficacious in migraine. Naratriptan and frovatriptan are the slowest-acting and least efficacious among all triptans. Clinical efficacy of triptan class of drugs is related more to the time to peak plasma level, than to the potency, half-life, or bioavailability of the drug. This is due to the requirement of prompt relief of symptom of migraine headache. This observation is consistent as seen in many clinical trials, indicating that faster-acting analgesics are more effective than slower-acting agents in migraine.

Disadvantages of 5-HT_1B/1D agonists:

Mono-therapy with a selective oral 5-HT_1B/1D agonist can not give rapid, consistent, and complete relief of migraine in all patients. Triptans are also not effective in migraine associated with aura unless given after the aura is completed and the headache initiated. Side effects are also common with triptans, though they are generally mild and transient. 5-HT_1B/1D agonists are contraindicated in individuals with a history of cardiovascular and cerebrovascular disease. Another major problem with triptans is recurrence of headache, which is an important limitation of triptan use and generally occurs at least occasionally in most patients treated with triptans.

Ergotamine preparations (non selective 5-HT₁ receptors agonists) stimulate 5-HT₁ receptors nonselectively. A small dose (nonnauseating dose) of ergotamine should be used since a dose that provokes nausea is too high and may intensify migraine. Except for a sublingual formulation of ergotamine, oral formulations of ergotamine also contain 100 mg caffeine (to enhance ergotamine absorption and possibly to add additional analgesic activity).