Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.

• Authors: Anna Barańczyk-Kuźma , Magdalena Kuźma , Marzena Gutowicz , Beatast Kaźmierczak , Jacek Sawicki
• Languages of publication: EN

Abstracts

EN

GST pi, the main glutathione S-transferase isoform present in the human brain, was isolated from various regions of the brain and the in vitro effect of tricyclic antidepressants on its activity was studied. The results indicated that amitripyline and doxepin - derivatives of dibenzcycloheptadiene, as well as imipramine and clomipramine - derivatives of dibenzazepine, inhibit the activity of GST pi from frontal and parietal cortex, hippocampus and brain stem. All these tricyclics are noncompetitive inhibitors of the enzyme with respect to reduced glutathione and noncompetitive (amitripyline, doxepin) or uncompetitive (imipramine, clomipramine) with respect to the electrophilic substrate. Their inhibitory effect is reversible and it depends on the chemical structure of the tricyclic antidepressants rather than on the brain localization of the enzyme. We conclude that the interaction between GST pi and the drugs may reduce their availability in the brain and thus affect their therapeutic activity. On the other hand, tricyclic antidepressants may decrease the efficiency of the enzymatic barrier formed by GST and increase the exposure of brain to toxic electrophiles. Reactive electrophiles not inactivated by GST may contribute in adverse effects caused by these drugs.

Keywords

EN

tricyclic antidepressants; human brain; glutathione S-transferase pi

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2004
• Volume: 51
• Issue: 1
• Pages: 207-212

Dates

published

2004

received

2003-09-23

revised

2003-12-02

accepted

2004-01-06

Contributors

author

Anna Barańczyk-Kuźma

• Chair and Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland

author

Magdalena Kuźma

• Department of Neurology and Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland

author

Marzena Gutowicz

• Chair and Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland

author

Beatast Kaźmierczak

• Chair and Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland

author

Jacek Sawicki

• Chair and Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland

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