Study sheds light on the working mechanism of ketamine
ketamine exerts its antidepressant effects and causes unwanted side effects
Researchers at the University of Texas Southwestern Medical Center (UT Southwestern) have identified a mechanism by which ketamine exerts its antidepressant effects and causes unwanted side effects. This discovery may help develop safer therapies for patients with depression.
The study appeared online Wednesday in Nature.
Ketamine is a drug that is mainly used in veterinary medicine as an animal tranquilizer but can also be used in human medicine as an anesthetic. Growing evidence shows that ketamine can quickly ease depression. So much attention is paid to the antidepressant effects of the drug. However, ketamine may also impair brain functions, leading to agitation, confusion, or hallucinations. Some researchers are making efforts to design novel drugs that possess ketamine's antidepressant but not hallucinogenic effects.
A team of researchers, led by a neurologist Lisa Monteggia at UT Southwestern, sought to determine the protein targets of ketamine in the brain. Ketamine has been classified as a noncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonist. Monteggia's team uncovered that ketamine initiates antidepressant reaction by blocking NMDAR whereas a metabolite of ketamine extends the duration of this effect. Additionally, the blocking of NMDAR also causes hallucinogenic responses.
NMDAR is a protein important for controlling brain function, such as memory and synaptic plasticity. The findings shed light on the molecular mechanisms of how ketamine works in the brain.
Ketamine has been shown to ease depression in patients who have not been helped by standard treatments. Moreover, it is able to stabilize depressed or suicidal patients in several hours, which is much more rapid than conventional antidepressants. But the potential hallucinogenic effects hinder its application in depression treatment.
Monteggia's team plans to further explore ketamine's working mechanisms in the future research. Their works are significant for depressed patients, especially for those resistant to existing therapies.
