Hi Onlyfacts, hope you get to see this and many thanks again for helping me out.
In order to further my understanding of the S1R I came across the following during my research which I think will be of interest to your good self. Hopefully if you copy and paste the next paragraph into your browser you will get to the link and article. If you fail to locate it let me know.
The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases, by Masatomo Ishikawa, Kenji Hashimoto
I copied some extracts from the article below, which are I find most interesting and relevant. Some of the wording below will probably sound very familiar to you. One that jumps out at me, takes me back to the Richard Smith MD Videos that lurk buried on the board if I get a minute I may dig them out.
Extracts from the article as below.
A relationship between sigma-1 receptors and depression was first identified by Matsuno and colleagues using the forced swimming test (FST), which is a standard animal model of depression. Sigma-1 ligands such as igmesine and SA4503 show antidepressive effects in the FST, and these effects are antagonized by the sigma
Interestingly, the antidepressant-like effect of SA4503 was achieved following a single administration of the drug. Subsequently, the rapid antidepressant-like action of SA4503 was replicated by different sigma-1 receptor agonists. Furthermore, electrophysiological studies demonstrated a rapid antidepressant-like action for sigma-1 receptor agonists
This finding is consistent with the sigma-1 receptor’s “receptor chaperone” mechanism, which ultimately results in neurite outgrowth. Taken together, these results suggest that sigma-1 receptor agonists have rapid antidepressant-like actions.
As described above, the unique ER protein sigma-1 receptors are assumed to serve as a regulator of ATP production and bioenergetics within the cell, and sigma-1 receptors may play a key role in the pathophysiology of some neuropsychiatric diseases. Furthermore, sigma-1 receptor agonists
have been implicated in the enhancement of neuroplasticity and cognitive functioning. The clinical potential of sigma-1receptor agonists is only just beginning to be explored. The primary therapeutic targets of sigma-1 receptor agonists in ongoing research include schizophrenia, major depression,
OCD, and AD.
As I recall, dex is always described as a weak sigma agonist. So that needs to be borne in mind when reading everything about possible roles of sigma agonists in treating any condition.
A weak sigma agonist is unlikely to be effective in those diseases right off the bat.
Hi Ray - That being the case we may find our selves being more fortunate than first realized. Being a NMDA receptor antagonist and a Sigma 1 agonist, to me that would suggest it works in two distinct ways but some how related, of course I do not know really but I think in the Richard Smith MD video, Richard Smith MD may have being saying just that. Perhaps in Dextromehorphan with this dual action it is little wonder that more than one indication could possibly benefit, hence the interest in the various studies. I’m also thinking that in the event the sigma 1 in Dextromehorphan was intensely potent the balance would be upset to a point of Dextromehorphan being unsafe.
Just touching back to you waiting for off label pain sales and wondering why you had not seen much of that. I think you answered your own question when you mentioned that 20/10 probably would not work. You obviously have no concerns with your 40/20 (2x20/10) dose at 12 hour intervals. As you would be aware of the QTc prolongation at the higher dose appears to be a concern of the FDA and probably prohibiting practitioners prescribing. From a layman’s point of view it is clear to me why the current MS Pain study is with 10Q.
Hopefully we shall soon be privy to some data in respect of the D/DM studies.