| Noradrenergic agonists and antagonists influence migration of cortical spreading depression in rat-a possible mechanism of migraine prophylaxis and prevention of postischemic neuronal damage. | |
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MedLine Citation:
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PMID: 15829916 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cortical spreading depression (CSD) is thought to be a neuronal mechanism that expands the penumbra zone after focal brain ischemia and that causes migraine aura. Both adrenergic agonists and antagonists significantly influence the size of the penumbra zone and decline the frequency of migraine. To study whether these compounds act by influencing CSD, we applied different drugs topically to an area of the exposed cortex of anesthetized adult rats and observed the migration of CSD-related DC potential deflections across the treated area. The adrenergic agonist norepinephrine (1 mmol/L) and the alpha(2)-agonist clonidine (0.56 mmol/L) blocked reversibly the migration of CSD. The beta-blocker propranolol (250 micromol/L to 1 mmol/L) dose-dependently diminished migration velocity or even blocked migration of CSD. The CSD blockade by the alpha(2)-antagonist yohimbine (1.75 mmol/L) was because of its action on inhibitory 5-HT(1A) receptors. None of the substances in the concentrations used had influence on regional cerebral blood flow or on systemic arterial blood pressure. The data suggest that the interference of these compounds with CSD may contribute to their beneficial therapeutic effect. The effect of beta-receptor antagonists in human migraine needs further exploration, since these drugs also work in migraine without aura. |
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Authors:
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Frank Richter; Oskar Mikulik; Andrea Ebersberger; Hans-Georg Schaible |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 25 ISSN: 0271-678X ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-24 Completed Date: 2005-09-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1225-35 Citation Subset: IM |
Affiliation:
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Institute of Physiology-Neurophysiology, Friedrich Schiller University Jena, Jena, Germany. FRIC@mti.uni-jena.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic Antagonists
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pharmacology* Adrenergic alpha-Agonists / pharmacology* Adrenergic beta-Antagonists / pharmacology Animals Blood Pressure / drug effects Brain Damage, Chronic / etiology, prevention & control* Brain Ischemia / pathology* Cerebral Cortex / drug effects, physiology Cerebrovascular Circulation / drug effects Clonidine / pharmacology Cortical Spreading Depression / drug effects* Drug Interactions Electrodes, Implanted Imidazoles / pharmacology Indoles / pharmacology Isoindoles Male Migraine Disorders / physiopathology*, prevention & control* Norepinephrine / pharmacology, physiology* Piperazines / pharmacology Propranolol / pharmacology Rats Rats, Wistar Receptor, Serotonin, 5-HT1A / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic Antagonists; 0/Adrenergic alpha-Agonists; 0/Adrenergic beta-Antagonists; 0/Imidazoles; 0/Indoles; 0/Isoindoles; 0/Piperazines; 112692-38-3/Receptor, Serotonin, 5-HT1A; 115338-32-4/1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; 118343-19-4/BRL 44408; 4205-90-7/Clonidine; 51-41-2/Norepinephrine; 525-66-6/Propranolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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