Ketamine is a very interesting compound. It acts at many different areas in the body. Traditional antidepressants, such as the reuptake inhibitors like Prozac, Cymbalta or Effexor, act by preventing the reuptake of serotonin or norepinephrine. These drugs work slowly. They don’t always work, with a response rate of only 60%. And they don’t continue to work, with a remission rate of as low as 28%.
Ketamine works differently, and at many different sites. The main one is the NMDA receptor, where ketamine blocks the action of the NMDA receptor. The NMDA receptor is located in the spinal cord, where the nerve enters the body. This receptor is important in causing the changes in the way the body handles pain in chronic pain, causing sensitization to painful stimuli, causing pain to occur after the cause of the pain (for example, stubbing your toe) is gone. The NMDA receptor can also leading to a decreased response to opioids.
Ketamine also causes the NMDA receptor to cause more brain derived neurotropic factor, or BDNF, to be made. BDNF is very important in treating depression. Traditional antidepressants work in part by increasing BDNF. Ketamine increases more effectively and more quickly than the traditional anti-depressants, which is likely why it is so effective in treating depression.
In terms of treating pain, ketamine works at many different sites. For example, it works at the Substance P, for pain, receptors, by making them less responsive to Substance P, leading to a decreased sensation of pain.
Ketamine also helps block a different receptor involved with pain perception, the muscarinic substance P receptor.
Another area of growing interest is glial cells, which are very important in controlling how nerves work. Ketamine influences the glial cells to help prevent sensitization and the continuation of pain when the cause of the pain is gone.
This is just a brief glance at all the ways ketamine can work. The important take away is that ketamine has many ways of acting and is effective for both pain and depression.