Direct inhibitory effect of fluoxetine on N-methyl-D-aspartate receptors in the central nervous system.
Biol Psychiatry
; 62(11): 1303-9, 2007 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-17659262
ABSTRACT
BACKGROUND:
Data accumulated in the last decade indicate that N-methyl-D-aspartate (NMDA) receptors might be involved in the pathophysiology of depression and the mechanism of action of antidepressants, although a direct inhibitory effect has been reported only in connection with tricyclic compounds, which interact with a wide range of receptors.METHODS:
Using whole-cell patch-clamp recording in rat cortical cell cultures, we investigated whether the selective serotonin reuptake inhibitor fluoxetine, which has a much better adverse effect profile, has a direct effect on NMDA receptors, and we compared its action to that of the tricyclic desipramine.RESULTS:
Both desipramine (concentration that causes 50% inhibition (IC(50)) = 3.13 microM) and fluoxetine (IC(50) = 10.51 microM) inhibited NMDA-evoked currents with similar efficacy in the clinically relevant low micromolar concentration range. However, in contrast to desipramine, the inhibition by fluoxetine was not voltage-dependent, and fluoxetine partially preserved its ability to associate with NMDA receptor in the presence of Mg(2+), suggesting different binding sites for the two drugs.CONCLUSIONS:
The fact that different classes of antidepressants were found to be low-affinity NMDA antagonists suggests that direct inhibition of NMDA receptors may contribute to the clinical effects of antidepressants.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Central Nervous System
/
Fluoxetine
/
Receptors, N-Methyl-D-Aspartate
/
Excitatory Amino Acid Antagonists
/
Antidepressive Agents, Second-Generation
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Biol Psychiatry
Year:
2007
Document type:
Article
Affiliation country:
Hungary