Document Detail


Non-competitive inhibition of GABA currents by phenothiazines in cultured chick spinal cord and rat hippocampal neurons.
MedLine Citation:
PMID:  2903473     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gamma-aminobutyric acid (GABA) inhibiting properties of several classes of antipsychotic medications were studied using gigaseal whole-cell voltage-clamp techniques in cultured chick spinal cord and rat hippocampal neurons. At doses above 1 microM trifluoperazine, chlorpromazine and thioridazine blocked GABA currents in a non-competitive fashion decreasing the maximal transmitter response without altering the half-maximal effective concentration. In contrast, haloperidol was ineffective against GABA at concentrations up to 100 microM. Among the agents studied trifluoperazine was the most potent GABA inhibitor with half maximal effect at 12 microM. Trifluoperazine (100 microM) also inhibited glycine-gated chloride currents in spinal cord neurons to an extent comparable to GABA (85 +/- 6% inhibition) but reduced glutamate currents by less than 35% in either spinal cord or hippocampal neurons.
Authors:
C F Zorumski; J Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience letters     Volume:  92     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  1988 Sep 
Date Detail:
Created Date:  1988-11-30     Completed Date:  1988-11-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  86-91     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antipsychotic Agents / pharmacology*
Cells, Cultured
Chick Embryo
Chlorpromazine / pharmacology
Hippocampus / cytology,  drug effects,  physiology*
Membrane Potentials / drug effects
Phenothiazines / pharmacology*
Rats
Spinal Cord / cytology,  drug effects,  physiology*
Thioridazine / pharmacology
Trifluoperazine / pharmacology
gamma-Aminobutyric Acid / pharmacology*
Grant Support
ID/Acronym/Agency:
MH00630/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Phenothiazines; 117-89-5/Trifluoperazine; 50-52-2/Thioridazine; 50-53-3/Chlorpromazine; 56-12-2/gamma-Aminobutyric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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