• N&PD Moderators: Skorpio | thegreenhand

MXE and opiate receptor affinity

I don't understand how you can equate getting 8 hours of sleep with having mu-agonism, or even stronger mu-agonism than ketamine. There are some studies out there that show ketamine works as a therapeutic tool for RLS and it clearly doesn't have much if any noticeable opioid effects. It's well known that NMDA-antagonists like ketamine decrease the required dose of mu-opioid agonists for equal analgesic properties as a higher dose of the opioid alone, but that doesn't mean this is the mu agonism at work. Some of the best opioid drugs used for severe RLS have NMDA-antagonist properties (tramadol, methadone, levorphanol, propoxyphene), giving speculative evidence that the NMDA-antagonism may be a pharmacological benefit to the opioid for treatment, or that nmda-antagonism alone like with ketamine could be enough to treat RLS symptoms. My neurologist has told me that propoxyphene was one of the better RLS opioid drugs when he could script it (better than non-nmda-antagonist opioids like hydrocodone), and being that propoxyphene is a shitty opioid, there must be once again some evidence that even having NMDA-antagonism alone can be enough to help produce a better nights sleep.

I really don't see any proof at all the MXE has any relevant mu-opioid agonism that would produce anything discernible to a human that could be called mu-opioid effects/opiate like pharmacodynamics. Seems like people just want to fantasize about combining the wonders of mu opioid agonism and nmda-antagonism dissociative into one drug. The mind is a powerful thing and can create something you feel validates a rationalization to assume so.

Clearly I made my statement based on my own experience, and nothing else. What is with people on this forum, any observation is chewed up if it doesnt square with what they believe! You did nothing more than state your observations and circumstantial evidence. You have not a single fact either.

If I had tried to make a statement and passed it off as research I could see a beat down being warranted but in this case I was very clear that my statement is my own observation and nothing more. Now go, and take your ugly mother with you.

I have no fantasy or agenda. I have made it very clear that I do not enjoy the effects of MXE in other posts. I simply have shared my own observations, which were unexpected, but clearly irrelevant in your lofty opinion.
 
Dont get you're panties in a bunch, I was merely trying to point out potential a possibility why MXE is helping you treat opioid detoxification induced sleep disorders (RLS and PLMS symptoms, which you described yourself). Secondary RLS (RLS that isn't idiopathic and associated with specific medical conditions or identifiable causes), like what is seen to present itself during opioid detoxification isn't just my observation, it is quite well known, and you pointed this it out as well. Also there are actually some studies/articles out there showing some efficiency of nmda-antagonists like ketamine in therapeutic treatment of RLS and PLMS, so once again this isn't just my own observations. I don't see how speculating that with some similar structural and pharmacodynamic characteristics with ketamine, MXE could produce similar therapeutic benefits for RLS and PLMS symptoms is a ridiculous conclusion.

In further discussion to reason why MXE's nmda-antagonism may produce potential benefits, neuropathic pain has been well studied, and classes of drugs with certain pharmacological properties have been shown to be beneficial in treatment of this type of pain. NMDA-antagonism is one of the pharmacological properties seen to be beneficial for neruopathic pain, giving another reason why ketamine would show some efficiency for RLS, given that RLS is a neurological disorder. RLS can present as strong neuropathic pain in more severe patients. Opioids with NMDA-antagonism are seen to have very high efficiency in treating those severe RLS presenting patients according to studies. Being that RLS is considered a neurological disorder as previously mentioned, and that nmda-antagonist opioids like tramadol, tapentadol, methadone, dextropropoxyphene, levorphanol, etc. are seen to be beneficial in treating other types of pain than nociceptive pain above traditional opioids, it can be concluded that it is in part due to their nmda-antagonist properties that they can treat RLS symptoms so well (some of these opioids do have SNRI effects that can be beneficial in neuropathic pain also - tramadol, methadone, levorphanol, etc.). None of this just my wild speculation, so it should be a reasonable possibility that MXE's nmda-antagonism could be why you are getting a higher quality of sleep. Unlike a lack of information supporting agonism at the mu-opioid receptor (only some leaning away from it, naloxone treatment), I feel there is a lot of published evidence supporting this conclusion.

I'm not trying to belittle you, just trying to present some information I feel is relevant, and could hold some validity. Sorry if it comes across that way. I honestly have been researching RLS and PLMS a lot recently, as I have refractory RLS, which I'm currently treating with methadone with success.
 
Dont get you're panties in a bunch, I was merely trying to point out potential a possibility why MXE is helping you treat opioid detoxification induced sleep disorders (RLS and PLMS symptoms, which you described yourself). Secondary RLS (RLS that isn't idiopathic and associated with specific medical conditions or identifiable causes), like what is seen to present itself during opioid detoxification isn't just my observation, it is quite well known, and you pointed this it out as well. Also there are actually some studies/articles out there showing some efficiency of nmda-antagonists like ketamine in therapeutic treatment of RLS and PLMS, so once again this isn't just my own observations. I don't see how speculating that with some similar structural and pharmacodynamic characteristics with ketamine, MXE could produce similar therapeutic benefits for RLS and PLMS symptoms is a ridiculous conclusion.

In further discussion to reason why MXE's nmda-antagonism may produce potential benefits, neuropathic pain has been well studied, and classes of drugs with certain pharmacological properties have been shown to be beneficial in treatment of this type of pain. NMDA-antagonism is one of the pharmacological properties seen to be beneficial for neruopathic pain, giving another reason why ketamine would show some efficiency for RLS, given that RLS is a neurological disorder. RLS can present as strong neuropathic pain in more severe patients. Opioids with NMDA-antagonism are seen to have very high efficiency in treating those severe RLS presenting patients according to studies. Being that RLS is considered a neurological disorder as previously mentioned, and that nmda-antagonist opioids like tramadol, tapentadol, methadone, dextropropoxyphene, levorphanol, etc. are seen to be beneficial in treating other types of pain than nociceptive pain above traditional opioids, it can be concluded that it is in part due to their nmda-antagonist properties that they can treat RLS symptoms so well (some of these opioids do have SNRI effects that can be beneficial in neuropathic pain also - tramadol, methadone, levorphanol, etc.). None of this just my wild speculation, so it should be a reasonable possibility that MXE's nmda-antagonism could be why you are getting a higher quality of sleep. Unlike a lack of information supporting agonism at the mu-opioid receptor (only some leaning away from it, naloxone treatment), I feel there is a lot of published evidence supporting this conclusion.

I'm not trying to belittle you, just trying to present some information I feel is relevant, and could hold some validity. Sorry if it comes across that way. I honestly have been researching RLS and PLMS a lot recently, as I have refractory RLS, which I'm currently treating with methadone with success.

And yet your long winded ;) post still contains nothing but your clever worded opinions and facts on unrelated drugs. Nothing of substance on the same subject yor jumped at me about. Yawn. My panties may not be folded before I put them away but they are dry and clean.
 
i think you're both right =p

many of the smarter minds in ADD think that MXE doesn't really produce any appreciable mu-agonism at normal doses

however, if MGS says that the MXE helps him sleep longer, then none of us can tell him he's wrong haha :)
 
And yet your long winded ;) post still contains nothing but your clever worded opinions and facts on unrelated drugs. Nothing of substance on the same subject yor jumped at me about. Yawn. My panties may not be folded before I put them away but they are dry and clean.

This is hardly just my opinons, but facts presented in easy to find articles by the way of googling. Everything I said helps correlates the potential relief of your noted opioid detoxification induce RLS and PLMS symptoms to pharmacological properties within MXE. I'm not desputing the existance of relief using these "long winded opinions", merely supporting the fact that you are getting relief through studied pharmacological properties of MXE that can be traced to other receptor systems than opioidergic ones (to nightwatch, like I said I'm not saying MXE isn't giving him relief, quite the contrary). My first post was clearly poorly written (I was pretty tired, and I noticed the next day when I reread it how it could have been hard to understand). I'm sorry about that, but this second post is a reasonable read with well presented ideas made in a neutral fashion. I'm not trying to put you down, or annoy you (which I am clearly doing). I want share my knowledge from reading hour and hours on the subject of RLS, and pharmacological theraputics used in treatment. When I get home from work I'll complie sources supporting all of my claims. If you want I can even give you the number of my neurologist, if you'd like a professional to repeat to you some of the stuff I've said...

Surprised how condescending your posts are, I would have thought you act a little more appropriately for a intellectual discussion when someone comments on a post of yours with reasonable statements, whether you agree with them or not. It would be better if you could refute my claims rather than ignore anything I said by saying they are personal opinions, when it's clear you haven't bothered to even consider the information presented could be factual in (or atleast show that you've considered it).
 
MGS said:
Clearly I made my statement based on my own experience, and nothing else. What is with people on this forum, any observation is chewed up if it doesnt square with what they believe! You did nothing more than state your observations and circumstantial evidence.

Not really. Splat gave a counter-example (ingestion of ketamine) where certain sensations can be misconstrued as opioid agonism in the absence of such effects. We're not saying that your experiences are worthless; rather, a certain skepticism is warranted whenever one tries to infer physiological activity from a single individual's subjective experiences.

And yet your long winded post still contains nothing but your clever worded opinions and facts on unrelated drugs.

Not really. Splat summarized research demonstrating the mechanism by which one could misconstrue some effects exerted by NMDA antagonism could be misconstrued as opioid agonism.

ebola
 
This may be a pointless post as it is just my experience and fairly limited at that and although I tried reading this whole thread I find that a good part of it is far above my head so it’s like reading a different language, but again here is my experience.

I take Suboxone on a regular basis at about 4mg a day total.

On one of my few breaks from the bupe using H I got very significant effects from small to moderate doses of MXE.

Then when I switched back to my Sub I found that the same dose that I used just days before did almost nothing and almost felt blocked. To this day I find using MXE with Suboxone to give very limited effects to the point that it almost seems pointless.

Again this is just my personal experience and it may be nothing but I just thought it might add to the subject as I experienced this then found this thread and thought there might be some correlation.
 
Methoxetamine is also a dopamine reuptake inhibitor which usually dilates the pupils so it's funny you get such elevated constriction at low doses.

Can you provide an example of a selective dopamine reuptake inhibitor that causes mydriasis? I always assumed that pupil dilation in stimulants was due to serotonergic or noradrenergic activity.
 
Off-topic:

I get severe mydriasis from recreational doses of DXM. We're talking through half of the next day from a mid-2nd plateau. Why might that be?

ebola
 
Off-topic:

I get severe mydriasis from recreational doses of DXM. We're talking through half of the next day from a mid-2nd plateau. Why might that be?

ebola

possibly due to DXM's effects as an SSRI?
 
DXM has mydriasis during the experience caused by the NMDA-antagonism (at least a lot of evidence points to this). SSRI's have been seen to cause mydrasis as well, so the serotonin action could be related. Even high doses of 5-htp according to wiki can be enough to cause some form of mydriasis. Opioid rebound can cause this (assuming this is talking about the effects after mu agonism, and kappa antagonism. Not sure about delta, as I Don't know to much about delta in the first place). Kappa opioid antagonism can cause mydriasis as well, seen with drugs like salvia. Just some thoughts... Maybe if there is some effect on NE post use there could be some mydriasis from that.

I'm at work so I can't spend much time looking up the specifics on DXMs pharmacology and I don't have any of my pharmacology books sitting around the office. This really intrigues me so I might spend some time before class this afternoon looking up some info and see if I can find anything. *writing a note in my pocket sized note book*
 
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