|Manufacturer:||Novartis Pharmaceuticals Corporation|
Considering structure/effect relationships, it has been demonstrated that methylation of the indole nitrogen in the lysergic acid ring of the alkanolamides fundamentally alters their pharmacologic behavior and is associated with inhibition or blockade of a great variety of serotonin-induced effects: 1. Methysergide maleate is 6 times more active than methylergonovine maleate in antagonizing the effect of serotonin on the rat uterus in vitro. 2. Greater inhibition of the serotonin-induced edema in the rat’s paw is revealed by the ED50 of 12.9 µg/kg for methysergide maleate as against 37.4 µg/kg for methylergonovine maleate (see following graph). 3. The more complex effects of serotonin on the cardiovascular system are equally subject to inhibition by methysergide maleate as is evident from the subsequent record of various circulatory parameters in the dog before and after administration of 10 µg/kg. Acute Toxicity LD 50 in mg/kg Mice Rabbits Rats Compound i.v. oral i.v. i.v. oral Methysergide maleate 185 581 28 125 2100 methylergonovine maleate 85 187 2.6 23 93 Chronic Toxicity Rats Daily Oral Doses mg/kg No.of Weeks Animals Tested Mortality 5 50 4/16 20 50 2/16 50 50 2/16 150 17 8/30 450 17 17/30 Control 50 1/16 Dogs Oral administration of 1, 2, and 5 mg/kg/day of methysergide maleate failed to produce any major signs of toxicity over a period of 6 months. *Trademark of Medical Economics Company, Inc. Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 REV: NOVEMBER 2000 T2000-69
With long-term, uninterrupted administration, retroperitoneal fibrosis or related conditions — pleuropulmonary fibrosis and cardiovascular disorders with murmurs or vascular bruits have been reported.
Patients must be warned to report immediately the following symptoms and to discontinue the drug: cold, numb, and painful hands and feet; leg cramps on walking; any type of girdle, flank, or chest pain, shortness of breath, or any associated symptomatology.
Should any of these symptoms develop, methysergide should be discontinued.
Continuous administration should not exceed 6 months.
There must be a drug-free interval of 3-4 weeks after each 6-month course of treatment.The dosage should be reduced gradually during the last 2-3 weeks of each treatment course to avoid “headache rebound.” The drug is not recommended for use in children.