Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mode of action of some classical and newer drugs used in the preventive interval treatment of migraine is discussed in the light of a modern theory of the pathogenesis of migraine headache. This headache is produced when two elements--a passive distension of the extracranial arteries and a lowering of the pain threshold of the receptors situated in the walls of the affected vessels--are present simultaneously. The main humoral factors involved in this phenomenon are plasma-kinins, serotonin and--to a lesser degree--histamine. The role played by serotonin which is released by the blood platelets at the onset of the attack is twofold: on the one hand, free serotonin increases the permeability of the capillaries, favouring transudation of plasmakinins, and lowers the pain threshold, while on the other hand, its increased excretion causes a secondary reduction in its plasma concentration, promoting hypotonicity of the extracranial vessels. Among the substances used for prophylactic interval treatment, some, such as dihydroergotamine, clonidine and the beta-blocking agents have a purely vascular site of action, maintaining--by various mechanisms--the tone of the extracranial arteries and thus reducing their lability. Methysergide and pizotifene have a chiefly indirect effect on the vessels, by potentiating the effect of catecholamines or helping to maintain free serotonin at a certain level. They act primarily against the humoral elements responsible for lowering the pain threshold: methysergide by inhibiting the release and blocking the effects of serotonin, by countering the potentiating effect of serotonin on the pain induced by plasmakinins and by inhibiting histamine release; pizotifene by inhibiting the release and blocking the effects of histamine, by blocking the effects of serotonin and by slightly inhibiting the peripheral effects of plasmakinins. Thus, the multifactorial pathogenesis of migraine helps to explain the effectiveness against migraine of substances possessing the most varied pharmacodynamic profiles.
 ...
PMID:[Mechanism of action of drugs currently used in the prevention of migraine]. 5 25

Nineteen patients obstinate with cluster headaches whose pain was not mitigated by standard treatment (Methysergide, caffeine, ergotamine preparation, phenobarbital and analgesics) underwent a double blind control study with single crossover for the evaluation of prednisone therapy. Compared to placebo, a single oral dose of prednisone in 17 cases produced sustained improvement. Maintenance administration of prednisone was also effective in decreasing the frequency of attacks; however a single dose of the steroid when headaches began was effective.
 ...
PMID:The treatment of cluster headaches with prednisone. 109 22

The effectiveness of five different serotonin antagonists in the prevention of migraine was compared in 290 patients followed for periods of up to three years. Methysergide 3-6 mg. daily was most effective, with 20% of treated patients becoming headache-free and a further 44% remaining more than "half improved." The corresponding figures for BC105 were 10% and 40%, respectively.The results with BC105 were significantly better than those with placebo (P<0.02). The total improvement rates with methdilazine (45%) and cyproheptadine (43%) were better than those with placebo (32%) but did not achieve statistical significance. A new preparation, methylergol carbamide maleate, which is chemically related to methysergide, did not give better results than placebo.
 ...
PMID:Comparative trial of serotonin antagonists in the management of migraine. 439 72

Classification, epidemiology, pathophysiology, and therapy of migraine, cluster, and muscle-contraction (tension) headaches are reviewed. Migraine headache is related to vasomotor changes and is often preceded or accompanied by neurologic symptoms, nausea, and vomiting. Ergot alkaloids are used in acute migraine episodes; products containing caffeine are sometimes used for synergy. Other agents including antiemetic and sedative drugs and a combination product containing isometheptene mucate , dichloralphenazone , and acetaminophen have been used. Methysergide is the drug of choice for migraine prophylaxis. Of all patients with cluster headache, 90% experience episodes that occur in series separated by intervals as short as one week or as long as 25 years, and the remaining 10% have chronic headache. Pain is unilateral, nausea and vomiting are rare, and there is no aura. Pathophysiology is thought to be similar to that of migraine. Supportive treatment includes drug therapy to improve sleep and avoidance of alcohol and vasodilating agents. Aerosol ergot preparations may be effective for treatment of acute episodes . Prednisone has been used both as an abortive agent and for prophylaxis, while ergotamine, methysergide, and lithium have been tried prophylactically. Chronic tension headache is a constant, tight, pressing, or bandlike sensation in the frontal, temporal, or occipital area that occurs daily. The deep, steady ache differs from the throbbing sensation of vascular headache. Constant overcontraction of scalp muscles may be a cause. Heat, massage, and stretching are used to alleviate excess muscle contraction. Tension headache has been treated with analgesics, nonsteroidal anti-inflammatory agents, muscle relaxants, and amitriptyline. Drug treatment of headache must be based on headache type and tailored to individual response. Bio-feedback may be useful in some patients when combined with drugs.
 ...
PMID:Classification, mechanisms, and management of headache. 637

Cyproheptadine is equipotent (IC50 = 41 to 45 nM) in blocking contractions of canine basilar artery segments induced by serotonin, norepinephrine, potassium, or calcium. Methysergide and amitriptyline display variable potencies in inhibiting contractions depending on the initiating agent. Propranolol, at concentrations to 10 micromolar, had minimal effect on vessel contractions. We conclude that the primary action of cyproheptadine in preventing induced contractions of the canine basilar artery is antagonism of calcium channels. This action is unique among drugs used for migraine prophylaxis and may have important implications for the treatment of headache and other neurologic disorders.
 ...
PMID:The calcium antagonist properties of cyproheptadine: implications for antimigraine action. 653 69

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.
Cephalalgia 1998 Sep
PMID:Methysergide. 979 94

Methysergide was used as a regular medication to prevent migraine in a series of 87 patients with frequently recurring severe attacks of three types, common, classical and cluster migraine, in a study conducted during a 30-month period. Results were classified as excellent, good, fair and nil. The total reporting excellent and good results was 50.6%. In a few patients the drug appeared to lose effectiveness in long-term treatment. Other investigators have described more favourable results, notably Friedman, who reported improvement in common migraine in 79% of patients and in cluster migraine in 90% of patients. Side effects were noted in 34.2% of patients and led to discontinuing the trial in 10.4%; these promptly subsided when the drug was withdrawn. Methysergide appears to be a useful additional agent for prevention of severe, frequently recurring migraine of common and cluster type. In this small series it had little effect on headaches of combined tension and vascular type.
 ...
PMID:METHYSERGIDE (SANSERT) IN THE PREVENTION OF MIGRAINE: A CLINICAL TRIAL. 1408 2

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.
 ...
PMID:EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. 1698 58

Migraine prophylaxis is a stepwise procedure with lifestyle advice followed by consideration of medications. Patients should be advised to try to maintain a regular lifestyle, with regular sleep, meals, exercise, and management of stress, perhaps through relaxation techniques or other ways that are sensible for them. If this regimen does not adequately control their migraines, preventatives are indicated. Patients can choose between evidence-based nutraceuticals such as riboflavin, feverfew, butterbur, or coenzyme Q10, or more traditional pharmacotherapeutics. Medicine choices are somewhat limited by what is available in each country, but from the full range, the medicines of first choice are beta-adrenoceptor blockers, flunarizine, topiramate, and valproic acid. Beta-adrenoceptor blockers are particularly useful in patients also suffering from hypertension or tachycardia. Following recent studies, topiramate has become a first choice for episodic as well as chronic migraine. It is the only prophylactic drug that may lead to weight loss, but it is sometimes associated with adverse cognitive effects. Valproic acid and flunarizine also have very good prophylactic properties. However, valproic acid is often associated with adverse effects, and flunarizine is unavailable in many countries, including the United States. If sequential monotherapies are ineffective, combinations of first-line drugs should be tried before advancing to drugs of second choice, which are associated with more adverse effects or have less well-established prophylactic properties. Amitriptyline should be used carefully because of its anticholinergic effects, although it is useful in comorbid tension-type headache, depression, and sleep disorders. Methysergide is very effective, but it has been supplanted or even made unavailable in many countries because of its well-described association with retroperitoneal fibrosis. Pizotifen has a slightly better safety profile but is unavailable in the United States. Aspirin is particularly useful in patients needing platelet inhibitors for other medical conditions, but the risk of gastrointestinal bleeding must be considered. The prophylactic properties of magnesium, riboflavin, and coenzyme Q10 are low at best, but their lack of severe adverse effects makes them good treatment options. Magnesium may be particularly useful during pregnancy. Lisinopril and candesartan were shown to be effective in single trials and are preferable in patients with hypertension. Acupuncture may be another alternative; although controlled trials have failed to differentiate its effect from placebo, it is at least innocuous. Botulinum toxin A is not effective in the prophylaxis of episodic migraine.
 ...
PMID:Update on the prophylaxis of migraine. 1832 96

Harold Wolff's theory of vasodilation in migraine is well-known. Less known is his search for a perivascular factor that would damage local tissues and increase pain sensitivity during migraine attacks. Serotonin was found to be among the candidate agents to be included. In the same period, serotonin was isolated (1948) and, because of its actions, an anti-serotonin drug was needed. Methysergide was synthesized from lysergic acid (LSD) by adding a methyl group and a butanolamid group. This resulted in a compound with selectivity and high potency as a serotonin (5-HT) inhibitor. Based on the possible involvement of serotonin in migraine attacks, it was introduced in 1959 by Sicuteri as a preventive drug for migraine. The clinical effect was often excellent, but 5 years later it was found to cause retroperitoneal fibrosis after chronic intake. Consequently, the use of the drug in migraine declined considerably, but it was still used as a 5-HT antagonist in experimental studies. In 1974 Saxena showed that methysergide had a selective vasoconstrictor effect in the carotid bed and in 1984 he found an atypical receptor. This finding provided an incentive for the development of sumatriptan. Bredberg et al. showed that methysergide is probably a prodrug for its active metabolite methylergometrine. Whereas methysergide is 'a clean drug', methylergometrine is 'a relatively dirty drug' with additional dopaminergic activity. The mechanism for the preventive effect of methysergide (methylergometrine) in migraine remains elusive. We describe the rise, fall and subsequent use as a third-choice drug of the first effective migraine prophylactic, methysergide.
Cephalalgia 2008 Nov
PMID:History of methysergide in migraine. 1864 39


1 2 Next >>