Ergot Alkaloids

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Information about Ergot Alkaloids

The triptans are a group of serotonin receptor agonists that are useful in the therapy of vascular headaches and migraine. 

Liver safety of Ergot Alkaloids

The triptans are generally used in low doses for a limited period of time and have not been associated with serum enzyme elevations, but some have been implicated in rare instances of clinically apparent, acute cholestatic hepatitis.

Mechanism of action of Ergot Alkaloids

The triptans (trip' tans) are synthetic serotonin receptor agonists that are used in the therapy of migraine and vascular headache.  Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine that has multiple actions, acting as a neurotransmitter and bioactive amine.  The diversity of actions of serotonin is partially due to the multitude of different serotonin receptors and their tissue location. 

Drug class for Ergot Alkaloids

There are at least 15 classes of serotonin receptors which have overlapping actions, but variable distribution and intracellular pathways of response to stimulation and inhibition.  The triptans are serotonin agonists with high affinity for the 5-HT1B and 5-HT1D receptors which are found on smooth-muscle cells of blood vessels.  Simulation of the 5-HT1D receptor results in constriction of intracranial blood vessels.  The triptans may also block the release of vasoactive peptides from perivascular trigeminal neurons through their action at presynaptic 5-HT1D receptors on nerve terminals.  Regardless, the triptans have been found to be effective in preventing or aborting migraine headaches with shortening of the period of pain and symptoms. 

Clinical use of Ergot Alkaloids

The triptans are considered “first line” agents for patients whose vascular headaches do not reliably respond to conventional analgesics.  They generally have a more rapid onset of action and fewer side effects than the ergot alkaloids. 

List of Ergot Alkaloids

Seven triptans are approved for use in the United States including almotriptan (al" moe trip' tan), eletriptan (el" e), forvatriptan (froe" va), naratriptan (nar"' a), rizatriptan (rye" za, sumatriptan (soo" ma) and zolmitriptan (zole" ma).  Generic formulations are available for most agents.  The short-acting triptans include sumatriptan, almotriptan, eletriptan, rizatriptan and rolmitriptan and generally provide relief within 30 to 60 minutes. 

The longer-activing oral triptans include naratriptan and frovatriptan which have a slower onset of action but may be better tolerated. Intranasal formulations may have a more rapid onset of action as do subcutaneous administered forms. Brand names, year approved, tablet or wafer size, usual dose and maximum daily recommended doses are shown in the Table.

Generic (Brand) Name Year Approved Tablet (or Wafer) Size Usual Initial Dose Maximum 24 Hour Dose
Almotriptan (Axert) 2001 6.25 and 12.5 mg 12.5 mg 25 mg
Eletriptan (Relpax) 2002 20 and 40 mg 40 mg 80 mg
Frovatriptan (Frova) 2001 2.5 mg 2.5 mg 7.5 mg
Naratriptan (Amerge) 1998 1 and 2.5 mg 2.5 mg 5 mg
Rizatriptan (Maxalt) 1998 5 and 10 mg 10 mg 30 mg
Sumatriptan (Imitrex) 1997 25, 50 and 100 mg* 50 mg 200 mg
Zolmitriptan (Zomig) 1997 2.5 mg and 5 mg** 5 mg 10 mg
  • Also available as nasal spray, transdermal patch and solution for injection. 
    • Also available in orally disintegrating tablets and as nasal spray. 

Dosage and administration for Ergot Alkaloids

Early therapy is recommended in patients with recurrent migraine, and typically the dose is repeated in 2 to 4 hours if relief has not occurred.  However, the total dosage should be limited to 2 to 3 doses per 24 hour period.  Parenteral and intranasal administration is helpful in patients with nausea and vomiting.  Chronic, long term use of triptans to prevent migraines has been studied, but is not currently approved. 

Side effects of Ergot Alkaloids

The seven triptans have similar side effect profiles which include “triptan sensations” characterized by tightening of the throat, chest, neck and limbs with paresthesias and hot or cold sensations.  Triptans may also cause flushing, headache, somnolence and fatigue. Rare but potentially severe adverse events include medication overuse syndrome, cerebrovascular and cardiovascular events such as myocardial infarction and stroke, serotonin syndrome and anaphylaxis. 

Migraine headache agents

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