Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Ergot is a parasitic fungal disease that is caused by the organism Claviceps purpurea and that has a particular prevalence for infecting rye plants. Ergot and the ergot alkaloids have been linked to epidemic poisonings that manifested as ergotism and resulted from consumption of rye. History shows that ergotism was more common in Germany and Russia than it was in the United Kingdom. The ratio of rye to wheat production and consumption was many times greater in the Eastern European countries compared with the United Kingdom and mirrors the higher incidence of ergotism seen in Eastern Europe.
Observations from ergotism epidemics at the close of the 19th century led to the use of ergot as a therapeutic agent. Ergot and ergot alkaloid derivatives are now used routinely in the treatment of migraine headaches and the prevention of postpartum hemorrhage.
Pharmacology
Ergot alkaloids are derivatives of the tetracyclic compound 6-methyergoline. The therapeutically important ergot alkaloids include ergotamine tartrate (Ergomar) and ergonovine (Ergotrate). Semisynthetic ergot alkaloid derivatives include dihydroergotamine and bromocriptine. The hallucinogen lysergic acid diethylamide (LSD) and the serotonin antagonist methysergide are structurally similar to the ergot alkaloids.
Ergotamine is chemically similar to the endogenous catecholamines and indolamines. Therefore, ergotamine has activity similar to noradrenaline, adrenaline, dopamine, and serotonin (5-hydroxytryptamine [5-HT]). When applied clinically, ergotamine behaves as an agonist at α-adrenergic, serotoninergic, and dopaminergic receptors. Through activity with these various receptors, ergot can exert powerful vasoconstriction. Vasoconstriction is one of the proposed mechanisms by which ergots treat migraine headaches.
The cytochrome P450 (CYP) system is responsible for extensive first-pass metabolism of ergotamine. As a result of the rapid first-pass metabolism, ergotamine ingested orally routinely results in low systemic drug concentrations. Despite limited bioavailability of ergotamine and a half-life reported between 2 to 4 hours, the vasoconstrictive effects of ergot have been reported to last for 24 hours or longer. Tight receptor binding of the drug, poorly defined metabolites of the drug that might have lingering biologic activity, and drug interactions that can slow ergot metabolism have been proposed mechanisms for the prolonged vasoconstrictive activity observed clinically.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here