Published online Nov 19, 2021. doi: 10.5498/wjp.v11.i11.981
Peer-review started: March 2, 2021
First decision: June 5, 2021
Revised: June 9, 2021
Accepted: August 23, 2021
Article in press: August 23, 2021
Published online: November 19, 2021
Core Tip: One of the main challenges in the advancement of antidepressant therapy is the establishment of safe and effective fast-acting antidepressants. Ketamine is a prototype for rapid-onset antidepressant responses. Agmatine has been shown to produce fast antidepressant-like effect by stimulating mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. Moreover, NLR family pyrin domain containing 3 and microbiota-gut-brain axis may be novel targets for fast antidepressant responses. These targets have also been postulated to play a role in the antidepressant effect of both ketamine and agmatine.