Comment · Tue, August 13, 2013 · Ceretropic
Memantine + Aniracetam have negated mechanisms of action. What happens when you take them?
Original post in this thread
willonz · 12 points
Enlighten me with your wisdom with this combination.
Have any of you gentlefolk intentionally tried this combination? What dosage at each substance?
I recently ordered some n=30 10 mg Memantine HCL and it just arrived in the mail today. I take .666 g of Aniracetam plus 500mg of Choline & Inositol daily.
To be specific, I would like to start taking Memantine HCL but have slight hesitance, because Memantine is a low-affinity voltage-dependent uncompetitive antagonist at the NMDA receptor; while Aniracetam and nootropic racetams in general are positive allosteric modulators at AMPA receptors. The specific mechanism of action per receptor protein is not specific, keeping in mind the conjoined effect of AMPAfication has on NMDA receptor availability, might have some correlation, thus hypothetically generating an asynergistic ('negated' in title) mechanism of action.
My hypothesis is that with an added low Ki antagonist to NMDA, would either downregulate AMPA or have no effect on such regulation, then any significant depolarization of NMDA would have a lesser effect on Aniracetam's positive excitetory modulation on NMDA, inducing a generally negated response between the two drugs.…
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · Ceretropic
.666 grams of aniracetam, huh? That's Satan's dose.
I have not taken them together, but I know the mechanisms. The fact that memantine is an uncompetitive antagonist that binds to an open-channel binding site, means that it can only bind once the magnesium blockage has cleared the channel. The magnesium block can only clear once the neuron reaches excitability. The neuron can only reach excitability if the AMPA receptors activate, allowing sodium (sometimes Ca^2+) to enter the cell and depolarize the charge. That allows the magnesium blockage to clear, calcium to pass through the NMDA channels, and for memantine to bind to the open-channel binding site and allosterically close the channel. Since aniracetam is a mild AMPA receptor positive allosteric modulator, this would lead to more transmission through the AMPA channels, but still allowing mematine to do it's job.
So I would think the synergism would be very good between the substances. The aniracetam would help facilitate the transmission of Ca^2+ into the neuron, but the mematine would help close the channel before it reached too high a concentration. They would not cancel each other out, nor would one overpower the other. If you were to take PCP, then there is really nothing aniracetam could do, since that is an uncompetitive channel blocker. However, memantine's mechanism is more natural.
Someone that has taken them together is going to have to comment on what it feels like, though. I have not acquired memantine myself just yet.
EDIT: PCP is actually an uncompetitive channel blocker, not a competitive antagonist.