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Antipsychotics inhibit TREK but not TRAAK channels
Susanne Thümmler1, Fabrice Duprat, Michel Lazdunski
1Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR 6097, Université de Nice-Sophia Antipolis, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
Biochemical and Biophysical Research Communications
|January 16, 2007
Summary
Antipsychotic drugs inhibit TREK channels, which are implicated in depression and schizophrenia. This finding suggests TREK channels may contribute to the therapeutic effects or side effects of these medications.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Schizophrenia affects 0.4% of the population, with current antipsychotics poorly addressing negative symptoms.
- TREK and TRAAK channels are potassium channels influenced by fatty acids and mechanical stress.
- TREK-1 channel inactivation in mice yields a depression-resistant phenotype, and antidepressants inhibit TREK activity.
Purpose of the Study:
- To investigate the direct effects of antipsychotic drugs on TREK and TRAAK channel activity.
- To explore the potential role of TREK channels in the mechanism of action or side effects of antipsychotics.
Main Methods:
- Electrophysiological recordings to measure TREK and TRAAK channel currents.
- Application of various antipsychotic drugs to assess their inhibitory effects.
- Determination of IC(50) values for drug inhibition.
Main Results:
- Different antipsychotic drugs directly inhibited TREK currents with IC(50) values ranging from approximately 1 to 20 microM.
- TRAAK channel activity was not affected by the tested antipsychotic drugs.
- TREK channels represent a novel target for antipsychotic drug action.
Conclusions:
- TREK channels may be involved in the therapeutic efficacy or adverse effects of antipsychotic medications.
- TREK channels could play a significant role in the underlying pathology of psychiatric conditions like depression and schizophrenia.
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