Posted by SLS on October 22, 2016, at 13:38:23
In reply to Re: Best alternative treatments for depression?, posted by Lamdage22 on October 22, 2016, at 11:00:36
> i wouldnt do ECT. Ketamine first definitely. I cant do it as i am schizo affective. I think anything "schizo" and Ketamine dont agree.
It would be interesting to know if you respond to the major ketamine metabolite, hydroxynorketamine (HNK). HNK does not interact with NMDA receptors nor does it produce a psychotic reaction when administered. Apparently, NMDA receptor antagonism is not required for ketamine to exert its antidepressant effects. It is more likely that the mechanism involves the activation of AMPA glutamatergic neurons. NMDA receptor antagonism does increase AMPA somewhat. However, this site is located upstream, and its effects are not very robust. When AMPA stimulation increases, BDNF (brain-derived neurotrophic factor) and mTOR (mammalian target of rapamycin) are increased in the hippocampus and prefrontal cortex. It may also be that increasing AMPA also increases catacholamine neurotransmitters (NE and DA) acutely. This might explain why the initial antidepressant effect is so rapid, but I'm not sure.
I would not hesitate to try HNK if it were to become available. As you comb through the literature, keep an eye out for drugs that stimulate AMPA receptor glutamatergic activity and BDNF production. Have you ever tried amitriptyline? What about sarcosine?
- ScottSome see things as they are and ask why.
I dream of things that never were and ask why not.- George Bernard Shaw
poster:SLS
thread:1092714
URL: http://www.dr-bob.org/babble/20160928/msgs/1092719.html