Inflammation and serotonin deficiency in major depressive disorder: molecular docking of antidepressant and anti-inflammatory drugs to tryptophan and indoleamine 2,3-dioxygenases.

ABSTRACT: The roles of the kynurenine pathway (KP) of tryptophan (Trp) degradation in serotonin deficiency in major depressive disorder (MDD) and the associated inflammatory state are considered in the present study. Using molecular docking in silico, we demonstrate binding of antidepressants to the crystal structure of tryptophan 2,3-dioxygenase (TDO) but not to indoleamine 2,3-dioxygenase (IDO). TDO is inhibited by a wide range of antidepressant drugs. The rapidly acting antidepressant ketamine does not dock to either enzyme but may act by inhibiting kynurenine monooxygenase thereby antagonising glutamatergic activation to normalise serotonin function. Antidepressants with anti-inflammatory properties are unlikely to act by direct inhibition of IDO but may inhibit IDO induction by lowering levels

SUBMITTER: Dawood S 

PROVIDER: S-EPMC9142829 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature