Ketamine: synaptogenesis, immunomodulation and glycogen synthase kinase-3 as underlying mechanisms of its antidepressant properties

摘要: Major depressive disorder is an extremely debilitating condition affecting millions of people worldwide. Nevertheless, currently available antidepressant medications still have important limitations, such as a low response rate and time lag for treatment that represent significant problem when dealing with individuals who are vulnerable prone to self-harm. Recent clinical trials shown the N-methyl-D-aspartate receptor antagonist, ketamine, can induce within hours, which lasts up 2 weeks, effective even in treatment-resistant patients. Nonetheless, its use limited due psychotomimetic addictive properties. Understanding molecular pathways through ketamine exerts effects would help developing novel agents do not evoke same negative side this drug. This review focuses specifically on three mechanisms relevant depression: synaptogenesis, immunomodulation regulation glycogen synthase kinase-3 activity.