Posted by Bob P (188.8.131.52) on August 16, 2000 at 16:39:09:
In Reply to: Sansert posted by Mary D on August 16, 2000 at 15:24:31:
Description: Methysergide is an oral, synthetic ergot alkaloid, structurally related to the oxytocic agent methylergonovine and to the potent hallucinogen LSD.
Methysergide is used prophylactically to reduce the frequency and intensity of severe vascular headaches. Although methysergide is an ergot alkaloid, it is a weak
vasoconstrictor and oxytocic. Methysergide is a more potent antagonist of peripheral serotonin receptors than other ergot alkaloids. Although methysergide and
sumatriptan both stimulate serotonin receptors centrally, methysergide is intended for prophylaxis while sumatriptan is indicated for treatment of an acute attack.
Methysergide was approved by the FDA in 1962.
Mechanism of Action: Although methysergide is an ergot alkaloid, it is a weak vasoconstrictor and oxytocic. Compared with other ergot alkaloids, methysergide has
greater antiserotonin activity. In contrast to ergotamine and dihydroergotamine, methysergide neither inhibits the reuptake of norepinephrine at nerve endings nor has a
direct vasoconstrictor effect. It also does not have appreciable oxytocic or alpha-adrenergic blocking effects at usual doses.
Methysergide is a highly competitive antagonist of serotonin (5-HT) in the periphery and may be a serotonin agonist in the CNS. Peripherally, the drug inhibits
serotonin-induced platelet aggregation, inflammation, and vasoconstriction. Serotonin is considered to be the chemical mediator controlling headaches, by either directly
or indirectly lowering the pain threshold. Platelet serotonin levels have been shown to increase before a migraine attack and decrease after the attack. In addition,
sumatriptan, an agent that successfully aborts migraine attacks, also stimulates CNS serotonin receptors. Thus, the serotonin agonist activity of methysergide in the CNS
appears to contribute to the prophylaxis of vascular headaches. Methysergide also inhibits histamine release from mast cells and greatly decreases prolactin secretion.
Pharmacokinetics: After oral administration, methysergide is rapidly absorbed and widely distributed throughout the body and possibly into breast milk. Onset of action
occurs within 1—2 days. Metabolism of the drug is mainly hepatic, producing methylergonovine and glucuronide metabolites. About 56% of a dose is excreted in the
urine unchanged and as metabolites. The drug has a half-life of about 10 hours.
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