Document Detail

Interaction of amfonelic acid with antipsychotic drugs on dopaminergic neurons.
MedLine Citation:
PMID:  1361248     Owner:  NLM     Status:  MEDLINE    
The effects of two inhibitors of dopamine (DA) reuptake, amfonelic acid and GBR 12909, on the clozapine- and haloperidol-induced increases in DA synthesis, release, and metabolism were investigated in the rat. In the striatum, as well as in the nucleus accumbens, the haloperidol-induced increase in tissue concentrations of dihydroxyphenylacetic acid (DOPAC) or the accumulation of dihydroxyphenylalanine (DOPA) was potentiated or unaltered, respectively, in rats treated with amfonelic acid. In contrast, amfonelic acid attenuated the stimulatory effects of clozapine on DOPAC concentrations and DOPA accumulation in both brain regions. GBR 12909 also differentially affected the haloperidol- and clozapine-induced increases in DOPAC concentrations. However, the clozapine-induced increase in DOPA accumulation in the median eminence was not significantly altered by treatment with amfonelic acid. The haloperidol-induced increase in the extracellular concentrations of DA and DOPAC in the striatum also was potentiated by amfonelic acid, whereas the increase elicited by clozapine was suppressed. The increase in extracellular DA produced by the administration of morphine or the coadministration of ritanserin, a 5-HT2 antagonist, and haloperidol also was potentiated by amfonelic acid. The ability of amfonelic acid to distinguish between the actions of clozapine and haloperidol on nigrostriatal and mesocorticolimbic DA neurons does not appear to be related to differences in the effects of the drugs on DA autoreceptors or 5-HT2 receptors. Moreover, the mechanism through which clozapine activates tuberoinfundibular DA neurons may differ from that which is involved in the activation of nigrostriatal or mesocorticolimbic DA neurons.
G A Gudelsky; E E Nwajei; K Defife; J F Nash
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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:  Synapse (New York, N.Y.)     Volume:  12     ISSN:  0887-4476     ISO Abbreviation:  Synapse     Publication Date:  1992 Dec 
Date Detail:
Created Date:  1993-01-19     Completed Date:  1993-01-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  304-11     Citation Subset:  IM    
Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio 44106.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Antipsychotic Agents / pharmacology*
Corpus Striatum / drug effects,  metabolism,  physiology
Dopamine / biosynthesis,  physiology*
Drug Interactions
Median Eminence / metabolism
Naphthyridines / pharmacology*
Neurons / drug effects*,  physiology
Neurotransmitter Uptake Inhibitors / pharmacology
Nucleus Accumbens / drug effects,  metabolism,  physiology
Piperazines / pharmacology
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Antipsychotic Agents; 0/Naphthyridines; 0/Neurotransmitter Uptake Inhibitors; 0/Piperazines; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 15180-02-6/amfonelic acid; 67469-78-7/vanoxerine

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