Document Detail

Effect of tacrine on in vivo release of dopamine and its metabolites in the striatum of freely moving rats.
MedLine Citation:
PMID:  8627574     Owner:  NLM     Status:  MEDLINE    
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.
U Warpman; X Zhang; A Nordberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  1996-06-27     Completed Date:  1996-06-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  917-22     Citation Subset:  IM    
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Atropine / pharmacology
Cholinesterase Inhibitors / pharmacology*
Corpus Striatum / drug effects*,  secretion
Dopamine / secretion*
Homovanillic Acid / metabolism
Mecamylamine / pharmacology
Rats, Sprague-Dawley
Receptors, Muscarinic / drug effects
Receptors, Nicotinic / drug effects
Tacrine / pharmacology*
Reg. No./Substance:
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

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