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Diazepam dependence prevented by glutamate antagonists.

Jamshyd said:
DXM is really not the most representatjve drug for NMDA-antagonist. In fact, it seems that this effect is a side-effect of it rather than the main one. DXM does a LOT more than just NMDA-antagonism.
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Is there a way to objectively know the power of an NMDA antagonist? What examples represent this class best? Does it vary depending on whether we are discussing benzo or opiate tolerance say...?
Also, do you think methadone would be a powerful enough antagonist to suppress any of the benzo w/d sxs? From what I gather, it is not.
Thanks.
I've heard of suboxone being used in benzo detox before (although it doesn't have this property AFAIK). I wrote of this in another thread.
 
Messing with glutamate in any way seems really scary to me. I know glutamate agonists can fuck you up for life. I forget exactly what they do in terms of long term effects, but they are very very neurotoxic. Along the lines in terms of toxicity as PMA or that other drug that gives instant parkinsons.

As for diazepam tolerance, I recently read somewhere that GABA antagonist therapy can completely reset the receptors. Theres another drug given to long term alcoholics that runs on the premise of restoring GABA function. Akin I guess to naloxone therapy for reparing opiate receptors.

I wonder if extreme low dose GABA antagonists in combination with a benzo would increase potency , like low dose naloxone does with opiates.

As for measuring NMDA antagonist potency, there are two main ways, subjectively, and with receptor binding affinity studies. I bet theres a list floating around here somewhere. Ketamine for the win though! That shit is silly as hell.

-lenses
 
HOC, since you're highly motivated about this, maybe you can figure something out that has had me puzzled for a while:

What is AZD-6765? I mean, what molecule is it. It's classified as an NMDA antagonist. A major pharmaceutical company has been pushing it through phase 1 and 2 studies for the past few years, trying to get it approved for treatment resistant depression and anxiety. It was formerly known as ARR15896.

The boon for you is that if it gets approval (which I suspect it will), you may soon be able to get a script for it to treat the same symptoms the clonazepam treated (even if off-label).

Here are it's entries at clinical trials dot gov
 
hookedonclonics said:
Is there a way to objectively know the power of an NMDA antagonist?
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It really depends on what you want from an NMDA antagonist. What do you mean by "power"?

But anyway, whatever it is that you are looking for, like I menioned above, the term "NMDA antagonist" is very, very broad, almost to an error. There is just way too much variety in this classification.

If you're looking for a Dissociative Anaesthetic, then the benchmarks are obviously Ketamine and PCP. However, do remember that these two also have other things on the side, such as dopaminergic and opioid activity.

It does seem that pure NMDA-antagonists are not fun. I believe that Dizocilipine is a pure NMDA-Antagonist with no secondary effects and reports of its effects range from "horrifying" to "boring as fuck" :).

By the way, Magnesium and Zinc work together as the "default" NMDA-antagonists in the body by acting as channel-blockers.

lenses said:
Messing with glutamate in any way seems really scary to me.
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Why? Are you one of those people who somehow "feel" certain things about certain Neurotransmitters? Me, personally, I always thought Glycine was kinda cute. It is small and submissive. Actually, I think it is secretly gay, but don't tell Glutamate... he's a bit insecure about his sexuality.

I know glutamate agonists can fuck you up for life.
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How?

I forget exactly what they do in terms of long term effects, but they are very very neurotoxic.
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ORLY? That's precisely why Ketamine was proven to protect against stroke-induced neuronal-damage, along with other things. (Example - one of several studies that prove the same point)

Along the lines in terms of toxicity as PMA or that other drug that gives instant parkinsons.
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Oh Please. Your ass was made for a lot of things, but talking isn't one of them. Keep that in mind next time.

As for diazepam tolerance, I recently read somewhere that GABA antagonist therapy can completely reset the receptors. Theres another drug given to long term alcoholics that runs on the premise of restoring GABA function. Akin I guess to naloxone therapy for reparing opiate receptors.
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No, because benzos, unlike opioids, do not act as direct agonists on the receptor, but rather as modulators, and so taking low doses of Flumazenil probably wouldn't help much.
 
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seep said:
HOC, since you're highly motivated about this, maybe you can figure something out that has had me puzzled for a while:

What is AZD-6765? I mean, what molecule is it. It's classified as an NMDA antagonist. A major pharmaceutical company has been pushing it through phase 1 and 2 studies for the past few years, trying to get it approved for treatment resistant depression and anxiety. It was formerly known as ARR15896.

The boon for you is that if it gets approval (which I suspect it will), you may soon be able to get a script for it to treat the same symptoms the clonazepam treated (even if off-label).

Here are it's entries at clinical trials dot gov
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I'm not that motivated!
I don't think it'll help me either; I'm strictly a recreational user who lost his way...:(
 
MeDieViL said:
He's mistaking nmda antagonist with the higly neurotoxic nmda agonists.
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Yes I believe this is correct. Lenses might want to take this opportunity to confirm he was confusing NMDA antagonists with NMDA agonists.
Although perhaps he cannot get up to sit at his computer due to the rectum tearing he suffered at the hands of Jamshyd in his last post.-DG
 
Thanks Jamshyd! Very informative.
By 'power' I meant the relative ability to suppress withdrawals/decrease tolerance.

edit: I do think you already answered this here:
The most useful ones seem to be those classed as "non-competitive" and "channel blocker" - which is what Ketamine and PCP are. I think the adamantanes are also classed here.
 
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hookedonclonics said:
I was speaking generally and wasn't directly referring to this particular study. I'm not at all familiar with AMPA antagonists... are there common examples?
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Oh, I just read that topiramate (Topamax) is an AMPA antagonist. A tree you may want to bark up at. You can probably get the Teva- or Mylan generic cheap in Canada. A topiramate/phentermine combo called Qnex is in phase III for appetite suppression. I wonder how these two synergize.
 
Jamshyd said:
I have personally used Ketamine to help with the initial phases of benzo withdrawal.

Not only did it work, but it also stopped my cravings AND caused my tolerance to actually go down considerably.

p.s. It also helped with opioid withdrawal, but not as much.
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How many times a day did you need to dose the ketamine?
 
hookedonclonics said:
I have to ask: did you take these during your benzo withdrawal and if so, were they effective? Did you try any others?

I've been tapering off of .75mgs of klonopin (now below .015mgs) and I also take methadone at 41mls/day. My symptoms have been minimal and I wonder if the NMDA antagonism of meth is enough to have that effect. Thoughts?
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Hey Hooked,
I too am beginning a klonipin taper/titrate, I take .5 four times a day. (Q.I.D.?).
Needless to say, any help is good help, so I'll be keeping an eye on this thread, and I'd welcome any info from anybody, that could help me. To show my sreiousness, I just self titrated off of 12mgs Suboxone daily, to zero, in approx. 90 days. Was on the above benzo, and clonidine, but nothing else except willpower and A.A.(I'm also an ex-alcoholic, 15 mos sober).

Thanks for your time, and I apologize if I am intruding in any way, as I know there are other threads for this type of question, also. Peace, Christopher
 
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