AMPA Antagonists - Effects?

[nAON]

Just wondering - seeing as AMPA and NMDA interact quite heavily, would blocking AMPA result in similar dissociative effects as an NMDA antagonist? Would something like NBQX be recreational, or at the least, psychoactive?

 

[Jonneh]

NMDA receptors have more of a modulatory function, so blocking them has limited (albeit dramatic) consequences. Taking an AMPA receptor antagonist might be pretty disabling, given that AMPA receptors mediate a number of basic processes: you probably wouldn't be able to move, for starters, and you might feel pretty stupid. Still, it probably wouldn't kill you at effective concentrations.

It would be psychoactive for sure, but probably not that fun; try inverting the effects of ampakines to get an idea. As for whether it would feel dissociative, I've no idea!

 

[endotropic]

Take a look at this AMPA receptor antagonist: http://en.wikipedia.org/wiki/Perampanel

Dizziness and somnolence/sedation/fatigue are the most frequent dose-related adverse events [...] It is designated as a Schedule III controlled substance by the Drug Enforcement Administration.

They don't put drugs in schedule III for no reason, so now the question: are the relevant effects mediated by AMPA antagonism, or some secondary action?

 

[...]

http://www.gpo.gov/fdsys/pkg/FR-2013-10-22/pdf/2013-24600.pdf

NSFW:

The HHS states that monkeys selfadministered
perampanel at rates
similar to or greater than those for
pentobarbital (Schedule II). These data
indicate that perampanel may have a
high psychological dependence liability.
It was demonstrated in rats that
cessation of administration of
perampanel produced withdrawal
symptoms similar to those produced
after cessation of diazepam (Schedule
IV) administration.
According to the HHS, a clinical
study of recreational drug abusers (with
histories of abuse of sedative hypnotic
and psychoactive drugs such as
ketamine (Schedule III) and alprazolam
(Schedule IV)) using ketamine
(Schedule III), alprazolam (Schedule
IV), and perampanel produced
subjective effects indicative of abuse
potential. The subjective effects
reported were ‘‘euphoria,’’ ‘‘high,’’ and
‘‘drug-liking.’’ For the measures of
‘‘floating,’’ ‘‘spaced out,’’ and
‘‘detached,’’ perampanel produced
similar responses to those of ketamine
(Schedule III) and greater responses
than those of alprazolam (Schedule IV).
The study used 8, 24, and 36 mg doses
of perampanel, 100 mg doses of
ketamine (Schedule III), 1.5 and 3mg
doses of alprazolam (Schedule IV), or a
placebo. Those that received 24 and 36
mg doses of perampanel reported
measures of ‘‘sedation,’’ ‘‘slowed
down,’’ ‘‘confused,’’ ‘‘clear crisp
vision,’’ and ‘‘attention span’’ at levels
similar to or greater than alprazolam
(Schedule IV) and greater than ketamine
(Schedule III). Forty-six percent of the
subjects reported euphoria-type adverse
events (AEs) with the 24 and 36 mg
perampanel doses, which was higher
than the rate reported for 3 mg
alprazolam (Schedule IV) (13 percent),

And so on (nsfw for length)

 

[Jonneh]

'euphoria-type adverse advents'. That's a new one!

 

[FrogWarrior]

I've wanted to try a selective AMPA antagonist for a long time now. I wonder why there are so many NMDA antagonists readily available, but no AMPA antagonists. Whether it produces enjoyable effects or not, it would be interesting to experiment with and probably has some useful applications.

 

[nAON]

Taking an AMPA receptor antagonist might be pretty disabling, given that AMPA receptors mediate a number of basic processes: you probably wouldn't be able to move, for starters, and you might feel pretty stupid.

This is what i'm worried about - could it perhaps [temporarily] shut down an essential brain function that depends on excitatory transmission?

 

[Jonneh]

There is seemingly conflicting evidence on this. DNQX produces 'no behavioural disturbance' in cats, whereas CNQX and BNQX inhibited locomotor activity in rats. Well, they seemed to survive, at least.

AMPAR functions may be compensated for by kainate receptors to some degree, but all of these drugs are antagonists for both AMPA and kainate receptors. Some of the effects of AMPAR antagonists are consistent with dissociation (analgesia, impaired spatial processing, reduced taste response) and probably fit with what is reported for parampanel, whatever else that may do. Glutamate antagonists might have anti-cancer effects too, albeit at the expense of cell viability (as is often the trade-off).

 

[dopamimetic]

Really interesting thread. I have thought that only NMDA antagonism would have the positive set of dissociative-associated effects, and regarding the AMPAkines and their effects on mood and cognition, that AMPA blockade would be as Jonneh said.

But then, it is the whole glutamate receptor complex involved and if it is true that the sub types do interact heavily, I could be wrong. NMDA antagonists in high doses are disabling too (they are anesthetics) but have completely different effects when taken in low dosages.

 

[Neuroprotection]

Just wondering - seeing as AMPA and NMDA interact quite heavily, would blocking AMPA result in similar dissociative effects as an NMDA antagonist? Would something like NBQX be recreational, or at the least, psychoactive?

It would certainly be psychoactive, though I doubt ampa antagonists are like NMDA antagonists in their affects. I have read a very interesting fact, ampa antagonists can block the psychotomimetic affects of NMDA antagonists.

 

[Ligaturd]

Interesting. The racetams definitely dampen the effects of dissociatives. I have read of Piracetam also having this effect but it isn't an ampakine to my knowledge. Pramiracetam and Aniracetam are ampakines however. I used to take Pramiracetam when I had to go out and function somewhat normally after doing a large dose or on a binge of MXE. It didn't completely take away the dissociative effects but I seemed to have a hell of a lot more motor control and my mind became somewhat lucid again.