[Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase].
Tricyclic antidepressants, amitriptyline, doxepin--derivatives of cycloheptadiene as well as imipramine and clomipramine, derivatives of dibenzazepine inhibit the activity of glutathione-S-transferase pi isolated from different regions of human brain (parietal cortex, frontal cortex, brain stem). The inhibitory effect of studied drugs depends more on their chemical structure than on brain localization of the enzyme. All tricyclics bind nonspecifically to the effector site of glutathione-S-transferase (GST). The obtained results indicate that the inhibitory effect of tricyclic antidepressants on brain GST may decrease the efficiency of the enzymatic barrier, which protects brain against toxic electrophiles, and contribute in their adverse effects. On the other hand, brain GST may decrease the therapeutic effects of tricyclic antidepressants by binding them as ligands.
Barańczyk-Kuźma
A
A
Katedra i Zakład Biochemii, Akademii Medycznej w Warszawie. akuzma@arnwaw.edu.pl
Sawicki
J
J
Kuźma
M
M
Jagiełło
J
J
D000639:Amitriptyline / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D001344:Autopsy; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002997:Clomipramine / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism; D004316:Doxepin / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D007099:Imipramine / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; D000639:Amitriptyline; D005982:Glutathione Transferase; D002997:Clomipramine; D007099:Imipramine