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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sumatriptan is a potent and selective agonist at a vascular serotonin1 (5-hydroxytryptamine1; 5-HT1) receptor subtype (similar to 5-HT1D) and is used in acute treatment of migraine and cluster headache. Following administration of sumatriptan 100mg orally, relief of migraine headache (at 2 hours) was achieved in 50 to 67% of patients compared with 10 to 31% with placebo in controlled clinical trials. In a comparative study, oral administration of sumatriptan 100mg consistently achieved significantly greater response rates than a fixed combination of ergotamine 2mg plus caffeine 200mg during 3 consecutive migraine attacks (66 vs 48% for first attack). Oral sumatriptan 100mg was also more effective than aspirin 900mg plus metoclopramide 10mg orally in a similar study. In the majority of controlled clinical trials, headache relief (at 1 hour after administration) was achieved in 70 to 80% of patients with migraine receiving sumatriptan 6mg subcutaneously compared with 18 to 26% of placebo recipients. Approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache, usually within 24 hours, but the majority of these patients responded well to a further dose of sumatriptan. Patients with cluster headache were treated for acute attacks with sumatriptan 6mg subcutaneously or placebo in 2 crossover trials. Headache relief was achieved within 15 minutes in 74 and 75% of patients receiving sumatriptan in these studies compared with 26 and 35%, respectively, with placebo. Patients receiving sumatriptan 12mg had a similar response rate as those receiving 6mg, but the higher dose was associated with an increased incidence of adverse events. Based on extensive safety data pooled from controlled clinical trials, sumatriptan is generally well tolerated and most adverse events are transient. The most frequently reported adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. Injection site reactions (minor pain and redness of brief duration) occur in approximately 40% of patients receiving subcutaneous sumatriptan, although the incidence appears to be markedly reduced when patients self-administer the drug with an auto-injector. Chest symptoms (mainly tightness and pressure) occur in 3 to 5% of sumatriptan recipients, but have not been associated with myocardial ischaemia except in a few isolated cases. Sumatriptan is contraindicated in patients with ischaemic heart disease, angina pectoris including Prinzmetal (variant) angina, previous myocardial infarction and uncontrolled hypertension, but is not contraindicated in patients with migraine and asthma. Data from long term studies in acute treatment of migraine and cluster headache suggest that sumatriptan remains effective and well tolerated over several months.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sumatriptan. A reappraisal of its pharmacology and therapeutic efficacy in the acute treatment of migraine and cluster headache. 751 61

The double-label flow cytometric analysis of peripheral serotonergic pathways of migraine and cluster headache on a monocyte model has been used to evaluate the activity of drugs with a selective activity on central vascular 5-HT1D receptors, such as sumatriptan, ergotamine and ondansetron. The results indicated that sumatriptan and ergotamine progressively increase the peripheral expression of 5-HT (5-hydroxytryptamine, serotonin). The increase obtained in migraine after ergotamine is more evident than that obtained in cases of cluster headache. Ondansetron produced a moderate increase in serotonergic expression only in cluster headache. The events that occur at intracranic neural and vascular level may cause the described changes of 5-HT expression on the monocyte model as an indirect, reflective, peripheral registration of central serotonergic variations during headache attack as well as during the drug-sustained recovery phase.
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PMID:Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan. 767 73

The 5-HT3 antagonism property of metoclopramide, acting on receptors presumably located in the trigeminovascular system, is the theoretical basis of its remarkable success, as a single intravenous agent, in the treatment of migraine attacks. The specific anti-migraine activity of oral metoclopramide is, most probably, applicable only when its plasma level is equivalent to 10 mg injected intravenously. The clinical effective dose of ergotamine, beginning from the minimal dose of 1 mg, correlates well with its affinity for 5-HT1B and 5-HT1D receptors, and the rank order of clinical potency of ergotamine is superior to sumatriptan. The presumed synergic power of drugs that interact with both 5-HT1 and 5-HT3 receptors is examined, in order to formulate a highly potent, low headache recurrence, oral combination.
Headache
PMID:Application of metoclopramide specificity in migraine attacks therapy. 792 30

I have discussed the pharmacokinetics, efficacies, and side effects of the various nonnarcotic drugs available for the treatment of patients who have headache. Sumatriptan, the newest one, is expensive but may be cost-effective for those who have failed traditional migraine treatment, who visit the ER frequently, who have potential for drug abuse, or who have to miss time from school or work due to the headache. Studies are in progress to compare sumatriptan with other available drugs such as DHE-45 and to determine its possible role in the prophylaxis of migraine. A new 5-HT1D receptor agonist with more efficacy and fewer side effects may be developed in the future. When sumatriptan and DHE-45 are contraindicated due to hypertension or coronary artery disease, other drugs such as metoclopramide, ketorolac, and butorphanol can be used as alternatives.
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PMID:Recent advances in the acute management of migraine and cluster headaches. 807

Sumatriptan, recently introduced for the treatment of migraine, heralds the beginning of a molecular era in the pharmacological treatment of migraine headache. An indole (non-ergot alkaloid) derivative with agonist properties at a receptor resembling the 5-HT1D subtype (so-called 5-HT1-like receptor), sumatriptan is the first antimigraine medication to exhibit receptor-selective properties. Clinical data indicate that sumatriptan relieves headache, nausea, and photophobia in a majority of acute migraine patients, and it possesses favorable side effect and safety profiles. Of great importance, sumatriptan acts through a novel mechanism that we now know is shared by dihydroergotamine and other useful compounds for the treatment of acute migraine headaches. In this summary, we briefly review the drug's mechanism of action and the emerging clinical experience with its use.
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PMID:SUMATRIPTAN: a receptor-targeted treatment for migraine. 838 98

The trigeminal nerve transmits headache pain from blood vessels of the pia mater and dura mater. Triggers for this pain are not well understood, but probably are multiple and largely chemical and develop within the brain parenchyma, the blood vessel wall, and the blood itself. These unknown triggers stimulate the trigeminovascular axons, causing pain and releasing vasoactive neuropeptides from perivascular axons. Released neuropeptides activate endothelial cells, mast cells, and platelets to then increase extracellular levels of amines, arachidonate metabolites, peptides, and ions. Hyperalgesia and prolongation of pain develop as a consequence, mediated by products from activated cells and injured tissue. Within postsynaptic brain stem neurons of the trigeminal nucleus caudalis, trigeminovascular activation stimulates the expression of an early immediate response gene c-fos. Both neurogenic inflammation and c-fos expression are blocked by sumatriptan and ergot alkaloids via prejunctional mechanisms involving putative 5-HT receptors closely related to the 5-HT1D subtype on trigeminovascular fibers. The mechanisms of action of sumatriptan and ergot alkaloids described herein are unrelated to the nature of the migraine trigger or to the contractile state of vascular smooth muscle.
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PMID:Neurogenic inflammation in the pathophysiology and treatment of migraine. 838 8

Migraine patients have chronically low systemic 5-HT, predisposing them to develop migrainous headache once an attack has been initiated. Changes in platelet 5-HT content are not causally related, but reflect similar changes at a neuronal level. Stimulation of vascular 5-HT1 receptors, probably located in the vessel wall within the dural vascular bed, may alleviate the headache and associated symptoms, but does not interact with earlier mechanisms within the pathophysiological cascade. These receptors are of an as yet unidentified 5-HT1 subtype, closely resembling, but not identical to 5-HT1D receptors. Activation of these receptors results in vasoconstriction, inhibiting depolarization of sensory perivascular afferents within the trigemino-vascular system and thus stopping the headache. Additional inhibition of the release of vasoactive neuropeptides may be involved, but seems to be of only secondary clinical importance.
Cephalalgia 1993 Jun
PMID:On serotonin and migraine: a clinical and pharmacological review. 839 42

Multiple 5-hydroxytryptamine (5-HT) receptors have been identified in humans. A subgroup of these receptors (designated 5-HT1 receptors) have been hypothesized to be involved in the mechanism of action of acute anti-migraine drugs. At present, this hypothesis cannot be tested directly in human tissues due to technical limitations. However, recent molecular biological advances have allowed for the development of assays employing cloned human 5-HT1 receptors expressed in cells by DNA transfection. This study analyzed the ability of ergotamine, dihydroergotamine, and 5-HT and sumatriptan to interact with the four known human 5-HT1 receptor subtypes. The four acute anti-migraine agents interacted with all 4 human 5-HT1 receptor subtypes with less than 1 microM affinity. However, drug affinities for the human 5-HT1B and 5-HT1D receptors correlate most closely with the rank order of clinical dosages used to treat a migraine attack. Therefore, these data indicate that human 5-HT1B and/or 5-HT1D receptors are likely to mediate the therapeutic efficacy of acute anti-migraine drugs.
Headache
PMID:Wolff Award presentation 1993. Anti-migraine drug interactions with cloned human 5-hydroxytryptamine1 receptor subtypes. 839 71

Efficacy with currently marketed antimigraine compounds is less than optimal. 311C90 is a novel and selective 5-HT1D receptor agonist in development for the acute treatment of migraine. It shows evidence of both central and peripheral activity within the trigemino-vascular system and it is rapidly absorbed following oral administration. In clinical studies in migraine patients, a headache response at 2 hours has been observed in 65-81% of patients at doses above 1 mg. Favourable response rates are reported as early as 1 hour post-dose and efficacy rates continue to improve up to 4 hours. Headache recurrence is reported by 25-35% of patients and 311C90 is also effective in relieving the non-headache symptoms of migraine.
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PMID:The clinical effectiveness of 311C90 in the acute treatment of migraine. 879 Oct 25

The ergot alkaloids are a family of chemical entities that have many pharmacologic effects. Their diversity results from their interaction with multiple receptors, their variable receptor affinity and intrinsic activity, and their variable organ-specific receptor access. Ergotamine tartrate (ET) was one of the first ergot alkaloids to be isolated. Dihydroergotamine (DHE) is synthesized by reducing an unsaturated bond in ergotamine (E); this modification results in a changed pharmacologic profile. Dihydroergotamine exhibits greater alpha-adrenergic antagonist activity and much less potent arterial vasoconstriction and emetic potential. Both E and DHE are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptor agonists. The vasoconstrictor activities of these ergot compounds have long been believed to be the basis of their clinical effects, but recent evidence suggests that their antimigraine action may result in part from their inhibitory effects on neurogenic inflammation and neuronal transmission and not from vasoconstriction. Improvements in assay methodology have provided more accurate determination of the pharmacokinetics of E and DHE. The long duration of action appears to result from active metabolites and tight tissue binding. Intranasal (IN) administration of DHE delivers adequate plasma concentrations of the drug without the need for parenteral administration and should further expand its role in migraine pharmacotherapy.
Headache 1997
PMID:The pharmacology of ergotamine and dihydroergotamine. 900 70


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