Ketamine Metabolite Linked to Rapid Antidepressant Effect

Model of crytalized ketamine molecule

Standard antidepressant therapies typically take two weeks or more to begin to act.

Ketamine is an anesthetic drug recently demonstrated to have a rapid antidepressant effect.

The mechanism for this effect is unknown. 

A recent mouse study of ketamine and metabolites of ketamine show some potentially groundbreaking insight for the treatment of depression.

This study found these significant findings:

• Ketamine like most organic compounds is made of boty an R and an S isomer that are mirror images 
• S ketamine is more potent in blocking NMDA receptors
• Blocking the metabolism of ketamine blocks the antidepressant effect suggesting an active metabolite is responsible for the physiological effect
• A key metabolite of ketamine named hydroxynorketamine appears to be the active agent in the antidepressant effect
• This active agent blocks the AMPA receptor rather than the NMDA receptor

These findings may lead to finding new drugs that can act like hydroxyketamine in producing a rapid antidepressant effect through the AMPA receptor.

The Science Daily link to this study can be found here.

Figure of ketamine is from the Wikipedia Commons File and authored by Ben Mills.

Follow the author on Twitter: @WRY999

Zanos, P., Moaddel, R., Morris, P., Georgiou, P., Fischell, J., Elmer, G., Alkondon, M., Yuan, P., Pribut, H., Singh, N., Dossou, K., Fang, Y., Huang, X., Mayo, C., Wainer, I., Albuquerque, E., Thompson, S., Thomas, C., Zarate Jr, C., & Gould, T. (2016). NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature DOI: 10.1038/nature17998