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Most "Potent" NMDA Antagonist

D

Dope_User

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In terms of both prescription and recreational drugs, as the topic states, which are the most potent NMDA antagonists? I know Lamictal (anti-convulsant, now approved for bipolar disorder), memantine (approved for treatment of Alzheimer's Disease), ketamine, PCP, and DXM all possess some NMDA antagonist properties. I'm just wondering if someone has a chart of table that compares the "relative strengths" of various NMDA antagonists such as those mentioned. I'd also like to know what other prescription NMDA antagonists exist and what are all the diseases/conditions for which they are prescribed (both those that they are approved for as well as "off-label" uses...please specify whether it is an approved or "off-label" use).
 
In relation to Ketamine's affinity for NMDA:
51144NMDA-antags.gif
 
Really what I'm trying to get at is ways of preventing/reducing opioid tolerance.

1. NMDA antagonists seem to have an effective.
2. Low doses of opiate antagonists have be effective.
From http://www.erowid.org/chemicals/opiates/opiates_info3.shtml
An interesting approach is the combination of opiates with the opiate antagonists naloxone or naltrexone in miniscule amounts. The combination of less than 0.001% of what would be a normal dose of the antagonist with an opiate allows a far greater response (�at least 50%�) to the opiate which in turn permits a much lower effective dose to be used. It is also said to prevent respiratory depression, tolerance and addiction. This approach has apparently been patented (Crain & Shen 1996) and is being commercially developed by Pain Therapeutics. [R.A.H. 2000; Crain & Shen 2000]
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3. From http://www.erowid.org/chemicals/opiates/opiates_info3.shtml
However, many people are unaware that both enhanced effectiveness of narcotic analgesics AND prevention or reversal of tolerance is readily achievable through the oral use of up to 200-250 mg of Proglumide [(DL)-4-Benzamido-N,N-dipropylglutaramic acid]. [See Ott 1999; Watkins et al. 1984]
Click to expand...

I'd like to hear more about this 3rd option, using Proglumide...this is the first time I've ever heard this mentioned.

Also, Blowmonkey, I really don't belong in the ADD forum, so could you clarify that table for me? Maybe use Ketamine's affinity for NMDA as the standard (100%.) and assign percentages to the other NMDA antagonists (i.e. 20%, 50%, etc.).
 
Progulumide itself has tolerance issues and has to be cycles on and off a few weeks i forget the exact number.
 
The above graph, shows the affinity of various NMDA antagonists (on the Y axis), and the amount of that drug needed for animals to think that it is dizocilpine (on the X axis).

As you can see, dizocilpine is the most potent, then TCP, (-)MK-801, PCP, Dextrorphan, SKF 10,047. Memantine is very low potency. Lower potency than any of those drugs mentioned (probably by around 5-10 times)
 
Is dextrophan some sort of isomer or active matabolist of DXM i'm guessing? is Dextrophan = DXO??? Doesn't magnesium play as a minor NMDA antagonist role?
 
FYI, dizocilpine is racemic MK-801 (or maybe it is the + isomer, I don't remember offhand).
 
Yeah, its the (+) isomer.

Dextrophan is DXO, its the primary(?) metabolite of DXM, and is a more potent NMDA receptor antagonist than DXM.

Magnesium plays a major role in blocking the NMDA ion channel, but it's part of normal physiological function, eating more magnesium (within reason) isn't going to make you trip out.
 
^^
Just in case someone was thinking of trying it with magnesium anyway,be warned - magnesium salts are osmotic laxatives, and the main thing you'll notice if you consume a dose of a magnesium salt is that you'll get a really bad case of the squirts
 
tenocylidine is pretty damn potent

and while magnesium has something to do with NMDA modulation, Ca 2+ is probably the more significant ion channel...
 
"magnesium has something to do with NMDA modulation, Ca 2+ is probably the more significant ion channel"

Do you mean through like PKC? Ca2+ is an the permiant ion, Mg2+ is the endogenous antagonistic ion.
 
I mean like S1 (and S2), in which the order of binding affinity to the former, with the aformentioned substances is something like

haloperidol>dextromethorphan>dizocilpine>dextrorphan>-3-PPP>PCP>tenocyclidine

i don't know what it is about those mystical sigmas I favor; i wish more study was devoted to them.
 
Here is marginally related question:
Are any exogenous NMDA antagonists notably psychoactive? Recreational?
Are any of them excitotoxins?

ebola
 
BilZ0r said:
You've completely lost me
Click to expand...

those compounds are sigma agonists, Ca2+ modulators, and NMDA antagonists; I was giving the order of their binding affinities to sigma 1 ligands.
 
Here's something very interesting (IMO) that goes along with NMDA antagonists and opiate tolerance.

I'm prescribed 300 mg Lamictal/day for Bipolar. My script ran out and I didn't call in the refill for about 2 days...basically, I went from 300 mg/day to nothing for about 5 days. Around the 4th day of no Lamictal, I just my normal 2 bags of heroin, felt almost nothing...shot 2 more and I was pretty high. So when I was off Lamictal (after 4-5 days) what it took approximately 1.5-2x the dose (that I took while on Lamictal) to get as high as before.

I do NOT think this is psychological at all. I wasn't even thinking about the Lamictal at any point when doing the H. In fact, I thought I just got crappy H and went back to the same dealer the next day and asked for a different "batch." The new batch had the same stamps as stuff I'd had before and 2 bags got me nice and high. I tried 2 bags on day 5 of no Lamictal and I didn't get that high. Now I knew something was wrong and my first instinct was that my tolerance had gone up. But I haven't been using much at all recently and when I was using more my tolerance never went up any where near that fast...my current guess is the Lamictal, which I've been back on for about 3 days and I'll try again in a week or so to see what happens. My theory, Lamictal (NMDA antagonist) works well to keep opiate tolerance significantly lower than it would be otherwise.
 
Ca2+? In what way? I find it very odd that you say that these compounds effects on the NMDA receptor ion channel complex are unreleated to their effect when the dosing of PCP and ketamine are nearly perfectly in symetry with there affinity for the NMDA channel.

Are NMDA receptor agonists excitotoxins? Yes, yes they are, very potently so, they would also be quite pro-convlusant, I wouldn't take one for $100.
 
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