Methysergide

Abstract

Methysergide is a semisynthetic ergot alkaloid ergometrine derivative, introduced in pharmacotherapy for migraine prophylaxis as a specific serotonin (5HT) receptor antagonist. Methysergide is not just a 5HT2 antagonist, it is also a 5HT1 agonist. Open and controlled studies attest to methysergide's efficacy. It may be more effective in resistant cases with a high attack frequency and may act synergistically with ergotamine and dihydroergotamine (DHE) for breakthrough attacks. Contraindications include pregnancy, peripheral vascular disorders, severe arteriosclerosis, coronary artery disease, severe hypertension, thrombophlebitis or cellulitis of the legs, peptic ulcer disease, fibrotic disorders, lung diseases, collagen disease, liver or renal function impairment, valvular heart disease, debilitation, or serious infection. Methysergide can induce retroperitoneal fibrosis and pleural and heart valve fibrosis with an estimated incidence of 1 in 5,000 treated patients. Therefore, it should be reserved for severe cases in which other migraine preventive drugs are not effective.

Conservation of structure, signaling and pharmacology between two serotonin receptor subtypes from decapod crustaceans, Panulirus interruptus and Procambarus clarkii

“…Interestingly, methysergide is an agonist at crustacean 5-HT 2␤ and 5-HT 1␣ . This drug is a functional antagonist of 5-HT 7Dro (Witz et al, 1990) and of vertebrate 5-HT 2 receptors but has agonist activity at some vertebrate 5-HT 1 receptors (Silberstein, 1998). The antagonist profiles of 5-HT 2␤ receptors from Panulirus and Procambarus are also very well conserved.…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Involvement of the 5-HT 2 receptor in migraine is suggested by the 5-HT 2 receptor antagonist methysergide, which is also a partial agonist at 5-HT 1 receptors, and is used for migraine prophylaxis in severe cases where other preventive drugs are not effective (Silberstein 1998). The 5-HT 2A/2C receptor genes have been studied as candidate genes for migraine (Buchwalder et al 1996), but no mutations in the deduced amino acid sequence of either receptor in the sample of migraineurs was observed.…”

Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology

“…The lenghty use of methysergide has led, with an estimated incidence of 1/5,000 treated patients, to RPF onset, sometimes together with mediastinal, pleural, pericardial and subendocardial fibrosis that implies a left-sided cardiac valve dysfunction (8,9).…”