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

100%

Baranczyk-Kuzma A., Kuzma M., Gutowicz M., Kazmierczak B., Sawicki J.

Acta Biochimica Polonica

2004

tom 51

nr 1

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 non- competitive inhibitors of the enzyme with respect to reduced glutathione and non- competitive (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.

Influence of tianeptine on melatonin homeostasis and psychosomatic symptoms in patients with irritable bowel syndrome

72%

Chojnacki C., Walecka-Kapica E., Mokwinska M., Romanowski M., Pawlowicz M., Chojnacki J., Klupinska G.

Journal of Physiology and Pharmacology

2013

tom 64

nr 2

Tricyclic antidepressants in the fatal poisoning of mother and her fetus. An unusual case report

72%

Klys M.

Acta Poloniae Toxicologica

1996

tom 04

nr 2

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Acta Poloniae Toxicologica

1 Journal of Physiology and Pharmacology

1 Baranczyk-Kuzma A.

1 Chojnacki C.

1 Chojnacki J.

1 Gutowicz M.

1 Kazmierczak B.

1 Klupinska G.

1 Klys M.

1 Kuzma M.

1 Mokwinska M.

1 Pawlowicz M.

1 Romanowski M.

1 Sawicki J.

1 Walecka-Kapica E.

1 2013

1 2004

1 1996

Wyniki wyszukiwania

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

Influence of tianeptine on melatonin homeostasis and psychosomatic symptoms in patients with irritable bowel syndrome

Tricyclic antidepressants in the fatal poisoning of mother and her fetus. An unusual case report