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)

The action of sumatriptan, putatively a selective 5-HT1D or 5-HT1-like receptor agonist which is effective in the treatment of migraine, has been studied on fresh human dural (middle meningeal) arteries. In low concentrations (10(-8)-10(-7) M) it was found to be a significantly stronger vasoconstrictor of dural arteries compared to cerebral and temporal arteries. However, its potency was less than that of 5-HT. The sumatriptan-induced vasoconstriction was antagonized by methiothepin (10(-9)-10(-8) M), but not by ketanserin (10(-7) M). The observations suggest that the sumatriptan-induced contraction of the dural artery is mediated via activation of 5-HT1D or 5-HT1-like receptors, whereas it does not appear to activate the 5-HT2 receptors.
Cephalalgia 1992 Aug
PMID:Sumatriptan is a potent vasoconstrictor of human dural arteries via a 5-HT1-like receptor. 132

Sumatriptan and the ergot alkaloids are useful tools for deciphering drug mechanisms in migraine and related headaches. Both neuronal and vascular mechanisms have been proposed on the basis of actions of 5-HT at receptors resembling the 5-HT1D subtype. In this Viewpoint article, Michael A. Moskowitz argues that blockade of neural transmission and the neurogenic inflammatory response provides a mechanism by which sumatriptan and ergot alkaloids alleviate vascular headaches. He postulates, with similar arguments, that sumatriptan and ergot alkaloids may block headaches that develop from meningovascular inflammatory disorders such as from viral and bacterial meningitis and from the sequelae of head injury.
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PMID:Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. 132 94

It is well established that cluster headache shows impaired functions at their neuroimmunomodulatory system level. Defect in receptor expression for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, a molecule with agonistic activity for 5-HT1D receptor, truncates cluster headache attacks in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients who are non responders to sumatriptan could present a block in their 5-HT receptor possibly due to specific autoantibodies for this receptor site.
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PMID:[The cluster headache: a clinical model of immunologic receptor pathology?]. 133 21

Neurogenic inflammation has been proposed as a possible pathogenetic mechanism for migraine and cluster headache. Antidromic stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and degranulation, vacuolation and increase in endothelial vesicle number within post capillary venules in rat dura mater. The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP) increase in the superior sagittal sinus following electrical trigeminal ganglion stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5-HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory activity is mediated by activation of 5-HT autoreceptors present on sensory fibers innervating blood vessels in dura mater.
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PMID:The trigemino-vascular system and migraine. 137 7

The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy.
Headache 1991 Apr
PMID:5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy. 164 76

Progress in migraine research has been rapid in recent years, from both the basic science and the clinical perspectives. A new internationally accepted headache classification with operational diagnostic criteria was published in 1988, eliminating much diagnostic uncertainty. More than a decade of study of regional cerebral blood flow (rCBF) has gradually shown a pathognomonic pattern of abnormalities, probably reflecting spreading cortical depression. Recently it has been shown that pain probably arises from excitation of perivascular pial arterial nociceptors. The innervation and receptor mechanisms of pial and extracranial arteries have been worked out in detail both in animal and humans. Involvement of calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) during migraine attacks has been demonstrated. A new and specific 5-HT1D receptor agonist has proved to be highly effective in treating migraine. Therefore, major research efforts recently have been concentrated on discovering the location and function of 5-HT1D receptors, extra- and intracranially. Thus, it is now possible to formulate useful neuroscientific research strategies aimed at clarifying migraine mechanisms.
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PMID:Migraine: a research field matured for the basic neurosciences. 170 30

Sumatriptan succinate, a 5-HT1D receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine.
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PMID:Treatment of acute migraine with subcutaneous sumatriptan. 165 6

The major finding of this analysis is that acute anti-migraine agents (e.g., ergots, sumatriptan) share high affinity for 5-HT1D receptors. This receptor appears to be present in certain intracranial blood vessels. It is also found on nerve terminals where it inhibits the release of 5-HT and other neurotransmitters. Theoretically, 5-HT1D receptor agonists may acutely inhibit the release of vasoactive and/or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In contrast, a number of prophylactic anti-migraine drugs share a relatively high affinity for 5-HT2 receptors in human brain. Although this receptor is also found in certain blood vessels, it is present throughout the nervous system. The receptor appears to mediate neuronal depolarizations at the cellular level. No hypothesis, at present, readily explains the effectiveness of prophylactic anti-migraine drugs based on this receptor. These data offer a novel approach to the analysis of anti-migraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. "Pure" drugs could be chosen which would essentially limit the number of possible sites of action for the drugs. For example, an agent which displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of the specific 5-HT receptor site in the pathogenesis of migraine. Further attempts to determine a common mechanism of action for effective anti-migraine agents should facilitate the elucidation of the pathogenesis of this neurological syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Headache 1990 Jan
PMID:The pharmacology of current anti-migraine drugs. 196 55

The potency of dihydroergotamine (DHE) was determined at 13 neurotransmitter receptors using radioligand binding techniques. DHE is a potent agent (i.e. affinity value less than 100 nM) at 5-hydroxytryptamine1A (5-HT1A), 5-HT1C, 5-HT1D, 5-HT2, dopamine2, alpha1- and alpha2-adrenergic binding sites. DHE displays moderate affinity (i.e. affinity values = 100 - 1000 nM) for beta-adrenergic and dopamine1 sites and is completely inactive at 5-HT3, muscarinic and benzodiazepine receptors. These results were then compared to similar data on sumatriptan (formerly called GR 43175), a novel acute anti-migraine agent. The only pharmacological property shared by both agents is high affinity for 5-HT1D and 5-HT1A receptors. Therefore, these data suggest that 5-HT1D and/or 5-HT1A receptors may play an important role in the pathophysiology of migraine.
Headache 1989 Jul
PMID:Comparative neuropharmacology of dihydroergotamine and sumatriptan (GR 43175). 254 33

It is well established that cluster headache shows impaired functions at the neuroimmunomodulatory system level. Defects in the expression of receptors for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, an agonist activity for 5-HT1D receptor, truncates cluster headache attack in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients which are non-responders to sumatriptan could present a block in their 5-HT receptor expression possibly due to specific autoantibodies for this receptor site.
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PMID:Is the unresponsiveness to sumatriptan in cluster headache related to an alteration in the 5-HT receptors? 751 79


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