Methysergide is an agonist of the serotonin (5-HT) receptor subtype 5-HT1 and an antagonist of 5-HT2 receptors.1,2 It binds to recombinant human 5-HT1A (KD = 23.44 nM), 5-HT1E (Ki = 229.09 nM), 5-HT1F (Ki = 33.88 nM), and rodent 5-HT1B receptors (KD = 1,513.56 nM).2 It also binds to recombinant human 5-HT2A (Ki = 2.69 nM) and 5-HT2C receptors (KD = 1.26 nM) and is an insurmountable antagonist at 5-HT2B receptors. It inhibits vasoconstriction induced by 5-HT (Item No. 14332) in isolated postmortem human basilar arterial spiral strips (pA2 = 8.07).3 Methysergide decreases external carotid blood flow in a dose-dependent manner in vagosympathectomized dogs, an effect that is inhibited by the 5-HT1B/1D receptor antagonist GR127935.4 It has antinociceptive activity in mouse models of pain induced by intrathecal injection of substance P (Item No. 24035), glutamate, NMDA (Item No. 14581), AMPA (Item No. 14571), or kainic acid.5 Methysergide reduces zymosan-induced paw edema in rats when administered at a dose of 10 mg/kg.6 Formulations containing methysergide were previously used in the prevention and treatment of vascular headaches.WARNING This product is not for human or veterinary use.