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Mechanisms of Action of the 5-HT1B/1D Receptor Agonists
Stewart J. Tepper, MD;
Alan M. Rapoport, MD;
Fred D. Sheftell, MD
Arch Neurol. 2002;59:1084-1088.
Recent studies of the pathophysiology of migraine provide evidence that
the headache phase is associated with multiple physiologic actions. These
actions include the release of vasoactive neuropeptides by the trigeminovascular
system, vasodilation of intracranial extracerebral vessels, and increased
nociceptive neurotransmission within the central trigeminocervical complex.
The 5-HT1B/1D receptor agonists, collectively known as triptans,
are a major advance in the treatment of migraine. The beneficial effects of
the triptans in patients with migraine are related to their multiple mechanisms
of action at sites implicated in the pathophysiology of migraine. These mechanisms
are mediated by 5-HT1B/1D receptors and include vasoconstriction
of painfully dilated cerebral blood vessels, inhibition of the release of
vasoactive neuropeptides by trigeminal nerves, and inhibition of nociceptive
neurotransmission. The high affinity of the triptans for 5-HT1B/1D
receptors and their favorable pharmacologic properties contribute to the beneficial
effects of these drugs, including rapid onset of action, effective relief
of headache and associated symptoms, and low incidence of adverse effects.
From the New England Center for Headache, Stamford, Conn (Drs Tepper,
Rapoport, and Sheftell); the Department of Neurology, Yale University School
of Medicine, New Haven, Conn (Drs Tepper and Rapoport); and the Department
of Psychiatry, New York Medical College, Valhalla (Dr Sheftell). Drs Tepper,
Rapoport, and Sheftell are consultants for GlaxoSmithKline, Merck, AstraZeneca,
and Pharmacia; conduct research for GlaxoSmithKline, Merck, AstraZeneca, Pharmacia,
Allergan, Elan, and OrthoMcNeill; and are on the speakers bureau for GlaxoSmithKline,
Merck, and AstraZeneca. Dr Rapoport is also a consultant for Abbott, Pfizer,
Forest Laboratories, Elan, and Bristol-Myers Squibb. Dr Sheftell is also a
consultant for Pfizer.
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