Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Patrycja Kleczkowska, Malgorzata Zaremba
5 citations
Ketamine, a derivative of phencyclidine, has anesthetic, analgesic, and antidepressant properties but is also a new psychoactive substance with psychedelic effects. Its recreational use has grown globally, becoming a common club drug that threatens public health by causing physical and psychiatric harm. Concurrent or sequential use with other drugs worsens health consequences. There are no specific treatments for compulsive drug-seeking in ketamine use disorder, and pharmacotherapy for side effects is limited and symptomatic. This chapter covers ketamine abuse history, proposes neural disinhibition mechanisms underlying addiction, details negative effects of long-term and recreational use on central and peripheral systems, and reviews adverse interactions from concomitant use.
Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Ouelhazi Afef, Rudy Lussiez, Molotchnikoff Stephane
1 citation
Ketamine alters orientation selectivity and functional connectivity among neurons in the primary visual cortex of mice and cats, indicating that antidepressant drugs can induce or model short-term neuroplasticity. The findings suggest that cortical processing is optimized and adapted to stimulus properties.
Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Bhargab Deka, Biswajit Dash, Alakesh Bharali et al.
1 citation
Ketamine has been used in medicine for over 50 years, yet its precise mechanism remains unclear. It induces dissociative anesthesia—a state of profound analgesia, amnesia, light sleep, immobility, and dissociation—and has been studied as a model for psychosis and as a rapidly acting antidepressant. The drug inhibits NMDARs, particularly in interneurons, and its hypnotic effects involve blocking NMDA and HCN1 receptors, while also modulating choline, amine, and opioid systems. Its lasting effects on chronic pain and depression may stem from a hyperglutamatergic state that increases structural synaptic connectivity. This review highlights ketamine's actions on multiple biochemical processes beyond NMDA receptors, explaining its diverse roles.
Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Tahani K. Alshammari, Sarah Alseraye, Nouf M. Alrasheed et al.
Sex differences in depression and its treatment are poorly understood. This review examines how male and female animals respond differently in pharmacological and genetic models of depression, focusing on the rapid antidepressant ketamine. The authors argue that considering sex as a key variable in preclinical research is essential for understanding the complex mechanisms of depression and treatment resistance. They aim to encourage neuroscientists to routinely include both sexes in studies of mood disorders to improve knowledge of pathological processes and develop more effective therapies.
Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Atamjit Singh, Preet Mohinder Singh Bedi
Ketamine, originally developed as a dissociative anesthetic, has recently gained attention for its rapid antidepressant effects, particularly in treatment-resistant depression and suicidal ideation. Unlike traditional antidepressants that take weeks to work, ketamine can produce clinical effects within hours. Its mechanism involves modulation of glutamate via NMDA and AMPA receptors, as well as downregulation of BDNF. This chapter reviews the mechanisms behind ketamine's antidepressant activity, along with its pharmacokinetics, toxicology, and ongoing clinical trials.
Ketamine Revisited - New Insights into NMDA Inhibitors
September 14, 2022
Maiko Satomoto
Electroconvulsive therapy (ECT) is highly effective for both major depressive disorder and bipolar disorder. Ketamine, an NMDA receptor antagonist, has antidepressant properties. This chapter reviews the literature on the effectiveness of ECT and ketamine, including whether ketamine-anesthetized ECT is more effective than conventional ECT, and whether ketamine can serve as an alternative to ECT for treatment-resistant depression.