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

Migraine is considered to be a primarily neurogenic disease. In this common headache syndrome beta-blockers are widely used as prophylactic drugs. In the meantime there is evidence for central beta-receptors. The effect of beta-blockers is considered to be based on a reduction of the increased sympathetic tonus and its influence on the intracerebral vessels. Beta-blockers--such as Atenolol, Metoprolol, Nadolol, Pindolol, Propranolol and Timolol which differ according to their intrinsic activity, their selectiv cardiac effects, their membran stabilizing ability, their hydro- or lipophily as well as according to their plasmaprotein binding capacity are used. Therefore, it is more likely that beta-blockers develop their effect through a stabilisation of the intrasynaptic serotonin-level in the serotonergic neurons of the brainstem.
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PMID:[Migraine and beta blocker. An overview]. 285 79

During the intervening years since metoprolol was first reviewed in the Journal (1977), it has become widely used in the treatment of mild to moderate hypertension and angina pectoris. Although much data have accumulated, its precise mechanisms of action in these diseases remain largely uncertain. Optimum treatment of hypertension and angina pectoris with metoprolol is achieved through dose titration within the therapeutic range. It has been clearly demonstrated that metoprolol is at least as effective as other beta-blockers, diuretics and certain calcium antagonists in the majority of patients. Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations. Addition of a diuretic may improve the overall response rate in hypertension. Several controlled trials have studied the effects of metoprolol administered during the acute phase and after myocardial infarction. In early intervention trials a reduction in total mortality was achieved in one moderately large trial of prolonged treatment, but in another, which excluded patients already being treated with beta-blockers or certain calcium antagonists and where treatment was only short term, mortality was significantly reduced only in 'high risk' patients. Overall results with metoprolol have not demonstrated that early intervention treatment in all patients produces clinically important improvement in short term mortality. Thus, the use of metoprolol during the early stages of myocardial infarction is controversial, largely because of the requirement to treat all patients to save a small number at 'high risk'. This blanket coverage approach to treatment may be more justified during the post-infarction follow-up phase since it has been shown that metoprolol slightly, but significantly, reduces the mortality rate for periods of up to 3 years. Metoprolol is generally well tolerated and its beta 1-selectivity may facilitate its administration to certain patients (e.g. asthmatics and diabetics) in whom non-selective beta-blockers are contraindicated. Temporary fatigue, dizziness and headache are among the most frequently reported side effects. After a decade of use, metoprolol is well established as a first choice drug in mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients. Further study is needed in less well established areas of treatment such as cardiac arrhythmias, idiopathic dilated cardiomyopathy and hypertensive cardiomegaly.
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PMID:Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. 294 80

Metoprolol slow-release tablets (Durules), 200 mg, given once daily in the morning were compared with placebo in the prophylaxis of classic migraine. The trial comprised eight Scandinavian neurologic centres and was designed as a double-blind cross-over study with 4 weeks' run-in, four weeks washout, and 8 weeks of either treatment. Seventy-seven patients with two to eight migraine attacks per month were entered in the trial, and 73 completed it. A total of 1119 attacks with aura symptoms and 374 without were recorded. Metoprolol was significantly better than placebo with regard to the total frequency of attacks (1.8 versus 2.5 attacks/4 weeks), mean duration of attacks (6.0 versus 8.0 h/attack), mean global rating, and consumption of analgesics per attack. Similar differences could be shown for attacks with aura symptoms alone, except for the duration of attacks. Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated.
Cephalalgia 1987 Dec
PMID:Classic migraine: effective prophylaxis with metoprolol. 332 69

In a double-blind, cross-over trial, the migraine prophylactic effect of the beta 1-adrenoceptor antagonist metoprolol was compared with that of clonidine. The dosage of metoprolol was 50 mg b.i.d. and of clonidine 50 micrograms b.i.d. Thirty-one patients were included; twenty-three completed the entire study. Six patients withdrew during clonidine treatment, one during metoprolol treatment and one during the wash-out period (placebo). Metoprolol had a significantly better migraine prophylactic effect than clonidine regarding such parameters as the attack frequency, the number of migraine days and the sum of intensity score. Compared to baseline (placebo), metoprolol decreased these parameters, while clonidine did not. Metoprolol, but not clonidine, also reduced the acute consumption of analgesics. No differences were found as regards side effects.
Cephalalgia 1985 Sep
PMID:Metoprolol v. clonidine in the prophylactic treatment of migraine. 389 70

A double-blind investigation with parallel groups was carried out in three Danish neurological clinics to evaluate the effect of metoprolol (Beloc, Betaloc, Seloken) versus placebo in migraine patients. 71 patients were included; 62 completed the study. The following parameters were used in the evaluation: frequency of headache attacks, days with migraine, severity score (days X intensity), and the consumption of pain-relieving tablets. The results of the study show that metoprolol 200 mg in Durules (a controlled release formulation) once daily is more effective regarding all evaluated parameters than placebo and that metoprolol is well tolerated.
Cephalalgia 1983 Dec
PMID:Prophylactic treatment of classical and non-classical migraine with metoprolol--a comparison with placebo. 664 Jun 52

In a double-blind trial 26 patients with essential hypertension were treated with nifedipine or placebo for 8 weeks, following a 4-week run-in-placebo period in all patients. The daily dosage of nifedipine during this phase was 10 mg 3 times daily. Metoprolol was then added to the therapeutic regimen of both groups for a further 12 weeks. Both nifedipine and metoprolol used as mono-therapy caused statistically significant reductions of arterial pressure. The addition of metoprolol to nifedipine tended to reduce blood pressure further, but blood pressures were not significantly lower than during nifedipine mono-therapy. Side-effects were few and only two patients had to be withdrawn during active therapy, one for headaches during nifedipine therapy, and another for asthma during metoprolol treatment. Combined therapy with a beta-adrenoceptor blocking agent, such as metoprolol, and a calcium antagonist with vasodilation properties, such as nifedipine, offers a theoretically interesting approach in the treatment of hypertension, even though the practical outcome in the present study probably suffered from an inadequate dose of nifedipine during the period of combined therapy.
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PMID:Effects of treatment with nifedipine and metoprolol in essential hypertension. 707 44

Metoprolol has not yet been systematically studied in terms of quality of life and incidence of adverse drug reactions (ADRs). Metoprolol is metabolized by polymorphic CYP2D6, therefore poor CYP2D6 metabolizers may be at higher risk of ADRs. Therefore, it is to be proven whether genotyping is useful to guide initial dose selection. In the ongoing UNAMET study, nonrandomized out-patients start treatment with metoprolol for various disorders. With the use of standard questionnaires, the patients are prospectively evaluated for common ADRs (headache, dizziness, tiredness, sleep disturbances, dyspnea, cold extremities, sexual dysfunction) and quality of life. The questionnaires are filled out before and until 6 weeks after initiating therapy; blood pressure and heart rate are also measured. The acquired data are then related to the patients' metoprolol dose and plasma concentrations, as well as to their metabolic ratio of metoprolol/alpha-OH-metoprolol and CYP2D6 genotype.
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PMID:[Rationale and methods of the UNAMET study (dose- and CYP2D6-genotype-dependent adverse drug reactions of metoprolol)--a contribution to quality improvement in pharmacotherapy]. 1564 32

Cortical spreading depression (CSD) is supposed to be the underlying biological basis of the migraine aura. Metoprolol was proven to be effective in migraine prophylaxis in clinical trials, but its mechanism of action has not been clarified yet. We studied direct effects of metoprolol on a continuous CSD induction model in rats. Six adult Wistar rats were anaesthetized with intraperitoneal thiopental (50 mg/kg). CSD was induced with application of 1 m KCL through a burr hole into the left frontal dura-mater, and recorded by an Ag/AgCl DC electrode on the left parietal dura-mater. After a basal recording of CSD induction during the first 40-min period, metoprolol (5 mg/kg) was infused within 4 min. Then DC recordings were maintained for a further 120 min. Any significant differences in total number and duration of CSDs before and after metoprolol administration were not detected. This study suggests that the mode of action of metoprolol in prophylaxis is not via direct CSD inhibition.
Cephalalgia 2007 Sep
PMID:Does metoprolol inhibit the cortical spreading depression? Acute effects of systematic metropol on CSD in rats. 1768 Oct 24

Migraine attacks are characterized as unilateral and pulsating headache with autonomic features. In about 15 % of Migraine patients the attacks are accompanied by, mostly visual, transient focal neurologic disturbances, the migraine aura. Migraine attacks of mild or moderate intensity should initially be treated with non-steroidal anti-inflammatory drugs (NSAID). A combination with prokinetic and antiemetic drugs like metoclopramide or domperidone has proved to relieve nausea and increase efficacy of the analgesic drugs. In case of severe attacks or lack of treatment efficacy the migraine attacks should be treated with 5-HT (1B/1D) receptor agonists (triptans). Patients that suffer under very frequent and/or very severe migraine attacks should receive a prophylactic treatment. Prophylactic drugs of first choice are Betablockers (Propranolol and Metoprolol), Topiramate and Flunarizine. Prophylactic treatment should be administered over a period of at least 6 - 12 months.
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PMID:[Treatment of migraine]. 1792 97