Methysergide

Treatment for overdose consists of removal of the offending drug by induction of emesis, or gastric lavage in the case of very recent intake, repeat dose administration of activated charcoal and catharsis. I.V. fluids may be given as a general supportive measure. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. (L1712)

Methysergide may reverse the analgesic activity of narcotic analgesics. Concurrent use with vasoconstrictor agents including ergot alkaloids, sumatriptan, and nicotine (eg smoking) may result in enhanced vasoconstriction.

/The authors/ report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. /Investigators/ reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, /investigators/ propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals.

A 28 year old housewife was admitted complaining of excrutiating pain in her feet. On examination her feet were pale and cold. Her hands were also cold but of normal colour. Her carotid, axillary, and femoral pulses were the only palpable peripheral pulses. She had suffered from migraine and duodenal ulceration for some years and had taken numerous drugs including propoxyphene, benzodiazepine derivatives, diclofenac, cimetidine, chlordiazepoxide, raubasine, sucralfate, ergotamine tartrate, and oxprenolol. The precise dosages and duration of these treatments could not be established, but we ascertained that she had been taking oxprenolol and ergotamine tartrate tablets for a considerable time before admission. Arteriography showed severe spasm of most parts of the femoral arteries, the distal parts of the brachial arteries, and the radial arteries. Intravenous infusion of heparin (500 units/hour) and dopamine (150-300 4g/min) resulted in moderate improvement in the circulation except in the left foot, which remained painful and developed a mottled appearance. A cannula was placed in the left femoral artery, and nitroglycerin (1 mg/hour) and heparin (500 units/hour) were infused. This caused a dramatic improvement. After 24 hours the peripheral pulses were palpable and the cannula was removed. Intravenous treatment was reduced over the next two days, and she made a satisfactory recovery.

A 21 year old policeman was admitted to hospital with progressive severe pain in his legs and feet of one week's duration. He had suffered from migraine for 10 years and had been taking methysergide (3 mg) and propranolol (120 mg) daily for two weeks. On examination his feet were pale, cold, and poorly perfused and only the femoral pulses were palpable in his legs. Aortography disclosed extreme bilateral narrowing of the superficial femoral arteries consistent with severe spasm. Intravenous infusions of 10% dextran 40 in saline (Rheomacrodex) and heparin (500 units/hour) and a lumbar epidural block with 1 % lignocaine failed to afford any improvement. Infusion of isoprenaline (1-2 ug/min) the next day resulted in mild improvement. Nevertheless, both feet gradually became gangrenous, and bilateral below knee amputations were performed six days after admission.

For more Interactions (Complete) data for METHYSERGIDE (7 total), please visit the HSDB record page.

There are no specific studies on the use of Methysergide in nursing mothers. Ergot alkaloids, in general, appear in mothers' milk. Methysergide is a semi-synthetic compound structurally related to ergotamine, and thus it may appear in breast milk. Ergot alkaloids have been reported to cause nausea, vomiting, diarrhea and weakness in the nursing infant and suppression of prolactin secretion and lactation in the mother. Because of the potential for serious adverse reactions in nursing infants from Methysergide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Methysergide as a serotonin antagonists acts on central nervous system, which directly stimulates the smooth muscle leading to vasoconstriction. Some alpha-adrenergic blocking activity has also been reported. Suggestions have been made by investigators as to the mechanism whereby Methysergide produces its clinical effects, but this has not been finally established, although it may be related to the antiserotonin effect. (A308, A2914, A2915, A2916)

Few cases of acute methysergide intoxication have been reported. The possible symptom complex is therefore not fully known. The following symptoms are based on these few case reports. Euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness have been reported in a child with a dose of 20-24 mg of methysergide. In adults, peripheral vasospasm, with diminished or absent pulses, coldness, mottling and cyanosis, has been observed at a dose of 200 mg. Ischemic tissue damage has not been reported in acute overdosage with methysergide.

/HUMAN EXPOSURE STUDIES/ The effects of acute oral administration of the antiserotoninergic drugs methysergide (3 mg) and metergoline (4 mg) on basal, submaximal (0.6 ug/kg i. m.) and maximal (6 ug/kg) pentagastrin-stimulated gastric acid secretion, as well as on basal and food-induced gastrin release, have been evaluated in healthy volunteers. Methysergide significantly increased basal and submaximal pentagastrin-stimulated gastric acid secretion, and metergoline significantly inhibited gastric acidity in all experiments. Basal and stimulated serum gastrin concentrations were not modified by either drug. The effect of methysergide on gastric acid secretion was opposed to that of serotonin and was probably dependent on its antiserotoninergic action...

/SIGNS AND SYMPTOMS/ Few cases of acute Methysergide intoxication have been reported. The possible symptom complex is therefore not fully known. The following symptoms are based on these few case reports. Euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness have been reported in a child with a dose of 20-24 mg of methysergide. In adults, peripheral vasospasm, with diminished or absent pulses, coldness, mottling and cyanosis, has been observed at a dose of 200 mg. Ischemic tissue damage has not been reported in acute overdosage with methysergide.

/CASE REPORTS/ Neuropathologic manifestations due to chronic ergotism are rare. /Investigators/ report the case of a 40-year-old patient who presented clinical signs and symptoms of a spinal lesion and also the symptoms of neuropathy involving the right sciatic nerve, more precisely the internal and external popliteal nerves, following ingestion of methysergide. Complete recovery was achieved with calcium blocker treatment. Ergotism should be considered in patients treated by ergot alkaloids presenting an atypical clinical manifestations.

/CASE REPORTS/ A 25-year-old woman sought medical attention because of iliocaval manifestations of retroperitoneal fibrosis while she was taking methysergide. Laboratory studies yielded substantially increased serum procollagen III levels and anticardiolipin antibodies accompanied with anti-beta(2) glycoprotein I, findings not previously described with this disorder. Clinical and laboratory manifestations resolved after cessation of methysergide therapy.

For more Human Toxicity Excerpts (Complete) data for METHYSERGIDE (18 total), please visit the HSDB record page.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

methysergide

Sansert®

Ergot alkaloids

Not Applicable

no-DILI-concern

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Oral administration of 1, 2, and 5 mg/kg/day of methysergide to dogs failed to produce any major signs of toxicity over a period of 6 months.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Daily doses as high as 5 mg/kg failed to elicit major toxic signs in dogs. Significantly increased mortality of rats was not achieved until dietary levels of 150 mg/kg per day were administered for 17 weeks. /Methysergide maleate/

FDA Pregnancy Risk Category: X /CONTRAINDICATED IN PREGNANCY. Studies in animals and or humans, or investigational or post-marketing reports, have demonstrated positive evidence of fetal abnormalities or risk which clearly outweighs any possible benefit to the patient./

MEDICATION

Methysergide is a synthetic derivative of the ergoline family, which occur naturally in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi like other ergoline alkaloids. Methysergide antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. It is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome and is sold under the brand names Sansert and Deseril in 2mg dosages. (L1918, L1924)

British patent 854,569 (1960); Hoffman, Troxler, US patent 3,218,324 (1965 to Sandoz).

... Lysergic acid hydroxybutylamide (methylergonovine)... methylation of indole N of latter compound yields 1-methyl-methylergonovine (methysergide).

Methysergide maleate, USP (Sansert), is avail in 2-mg tablets. /Maleate/

Deseril, Desernil, Desernyl, Deseryl

Methylation in the number 1 position of the ring structure enormously enhances the antagonism to serotonin which is present to a much lesser degree in the partially methylated compound (methylergonovine maleate) as well as profoundly altering other pharmacologic properties.

/Methysergide/ ... is a congener of sysergic acid diethylamide (LSD).