Inhibition effects of some antidepressant drugs on pentose phosphate pathway enzymes

Environ Toxicol Pharmacol. 2019 Nov:72:103244. doi: 10.1016/j.etap.2019.103244. Epub 2019 Aug 16.

Abstract

The glucose metabolism in the pentose cycle is essential to the source of NADPH. Deficiency of these enzymes have been linked to depression and psychotic disorders. Depression is an increasingly prevalent mental disorder which may cause loss of labor. Antidepressant drugs are commonly employed in treatments of mood disorders and anxiety treatment. The purpose of this study is to investigate the effects of aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol on the activity of 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD) enzymes purified from human erythrocytes. It was found that aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol show effective inhibitor properties on purified G6PD and 6PGD enzymes. The IC50 values of these drugs were found in the range of 26.34 μM-5.78 mM for 6PGD and 16.26 μM-3.85 mM for G6PD. The Ki values of the drugs were found in the range of 30.21 ± 4.31 μM-4.51 ± 1.83 mM for 6PGD and 14.12 ± 3.48 μM-4.98 ± 1.14 mM for G6PD. Usage of drugs with significant biological effects may be a hazard in some conditions.

Keywords: 6-phosphogluconate dehydrogenase; Antidepressant drugs; Enzyme inhibition; Glucose-6-phosphate dehydrogenase.

MeSH terms

  • Antidepressive Agents / pharmacology*
  • Aripiprazole / pharmacology
  • Citalopram / pharmacology
  • Erythrocytes / drug effects*
  • Erythrocytes / enzymology
  • Glucosephosphate Dehydrogenase / antagonists & inhibitors*
  • Haloperidol / pharmacology
  • Humans
  • Mirtazapine / pharmacology
  • Pentose Phosphate Pathway / drug effects*
  • Phosphogluconate Dehydrogenase / antagonists & inhibitors*

Substances

  • Antidepressive Agents
  • Citalopram
  • Aripiprazole
  • Mirtazapine
  • Phosphogluconate Dehydrogenase
  • Glucosephosphate Dehydrogenase
  • Haloperidol