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Competitive vs. Noncompetitive NMDA Antagonists

Ham-milton

Ham-milton

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I was wondering if anyone was aware of the effects produced by competitive NMDA antagonists. I assume such a thing exists, but the only recreational dissociatives I've seen are noncompetitive. Is there a reason?
 
Ham-milton said:
I was wondering if anyone was aware of the effects produced by competitive NMDA antagonists. I assume such a thing exists, but the only recreational dissociatives I've seen are noncompetitive. Is there a reason?
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there are several sites of action on the NMDA glutamate receptor, the dissociative non competitive antagonists are ion channel blockers hence non competitive. The low affinity ion channel blockers seem to have greater medical utility as they are not dissociative.

There is a lot of work being done on othosteric (glutamate) and allosteric (glycine) site modulators for NMDA receptors some of which would seem to have potential as antidepressants and neuroprotective agents. So far the direct glutamate site agonists and antagonists have serious problems. Agonists are often convulsant neurotoxins.
 
Thanks, that makes more sense to me.

Okay, so with the 2',4'-dialkyl methaqualone analogues being AMPA agonists, they're referring to the AMPA-site of the glutamate receptor? Agonists at the AMPA site are also convulsants, right?

Are there any known euphoriant properties for agonists or antagonists at other glutamate sites?
 
Ham-milton said:
Thanks, that makes more sense to me.

Okay, so with the 2',4'-dialkyl methaqualone analogues being AMPA agonists, they're referring to the AMPA-site of the glutamate receptor? Agonists at the AMPA site are also convulsants, right?

Are there any known euphoriant properties for agonists or antagonists at other glutamate sites?
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AMPA is a sub type of Glutamate receptor, the others being NMDA, and Kainic acid
I expect within the AMPA receptor there are multiple binding sites.

do we know that dialkylmethaqualones are AMPA agonists?

as for euphoriant activity I do not know. I was taught that it is a bad idea to directly agonise any glutamate receptor as they are the workhorse of the brain, it is better to modulate them allosterically or by using monoamine receptors which act more to regulate overall brain activity levels.
 
Oh wait, I have it backwards, they're noncompetitive AMPA antagonists. I've been confused for days!
 
Funny to hear that you were confused for days ;) but where does your assumption come from that methaqualone binds to AMPA or any other glutamate receptor? Could you point out a ref for me, plz? I'd like to read a bit about this as MQ is one of my TOP5 on the schedule list.

Thankfully,

Murphy
 
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