The pharmacology of ergotamine and dihydroergotamine.

Abstract:

:The ergot alkaloids are a family of chemical entities that have many pharmacologic effects. Their diversity results from their interaction with multiple receptors, their variable receptor affinity and intrinsic activity, and their variable organ-specific receptor access. Ergotamine tartrate (ET) was one of the first ergot alkaloids to be isolated. Dihydroergotamine (DHE) is synthesized by reducing an unsaturated bond in ergotamine (E); this modification results in a changed pharmacologic profile. Dihydroergotamine exhibits greater alpha-adrenergic antagonist activity and much less potent arterial vasoconstriction and emetic potential. Both E and DHE are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptor agonists. The vasoconstrictor activities of these ergot compounds have long been believed to be the basis of their clinical effects, but recent evidence suggests that their antimigraine action may result in part from their inhibitory effects on neurogenic inflammation and neuronal transmission and not from vasoconstriction. Improvements in assay methodology have provided more accurate determination of the pharmacokinetics of E and DHE. The long duration of action appears to result from active metabolites and tight tissue binding. Intranasal (IN) administration of DHE delivers adequate plasma concentrations of the drug without the need for parenteral administration and should further expand its role in migraine pharmacotherapy.

journal_name

Headache

journal_title

Headache

authors

Silberstein SD

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

S15-25

eissn

0017-8748

issn

1526-4610

journal_volume

37 Suppl 1

pub_type

杂志文章,评审

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