| Effect of tacrine on in vivo release of dopamine and its metabolites in the striatum of freely moving rats. | |
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MedLine Citation:
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PMID: 8627574 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of tacrine (THA) on extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were investigated in the striatum of freely moving rats, using a microdialysis technique in which tacrine was administered locally via the microdialysis membrane. THA in concentrations of 10(-8) to 10(-5) M, significantly elevated the levels of the DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, whereas a significantly increased content of extracellular DA was observed at higher concentrations of THA (10(-3) to 10(-2) M). Local administration of the muscarinic antagonist atropine (10(-6) M) or the nicotinic antagonist mecamylamine (10(-5) M) both prevented the effects of THA on DA and its metabolites. In vitro receptor binding studies showed that THA displaced the binding of muscarinic antagonists [3H]pirenzepine (IC50, 2.1 +/- 0.4 microM) and [3H]AFDX 384 (IC50, 3.4 +/- 0.2 microM) equally in striatal tissue, suggesting that THA binds with equal affinity to M1 and M2 muscarinic receptor subtypes. THA showed a 20-fold lower affinity to high-affinity nicotinic receptors compared with muscarinic receptors when determined by [3H]cytisine competition curves. The study indicates that THA enhances monoamine neurotransmission in the rat striatum, probably via an interaction with both muscarinic and nicotinic heteroreceptors. |
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Authors:
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U Warpman; X Zhang; A Nordberg |
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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: The Journal of pharmacology and experimental therapeutics Volume: 277 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1996 May |
Date Detail:
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Created Date: 1996-06-27 Completed Date: 1996-06-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 917-22 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Biosciences, Uppsala University, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3,4-Dihydroxyphenylacetic Acid
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metabolism Animals Atropine / pharmacology Cholinesterase Inhibitors / pharmacology* Corpus Striatum / drug effects*, secretion Dopamine / secretion* Homovanillic Acid / metabolism Male Mecamylamine / pharmacology Microdialysis Rats Rats, Sprague-Dawley Receptors, Muscarinic / drug effects Receptors, Nicotinic / drug effects Tacrine / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Cholinesterase Inhibitors; 0/Receptors, Muscarinic; 0/Receptors, Nicotinic; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 321-64-2/Tacrine; 51-55-8/Atropine; 60-40-2/Mecamylamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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