Donepezil reverse dissociative effect of Memantine

[MiowCat]

Hey, Community.

At my several experiences, Memantine has dissociative effect in high dose ( >80 mg),

but in the last trip when I add 10 mg Donepezil ( as AchEI) 4 hour after Memantine administration, Donepezil was reversing Memantine hallucinogenic effect immediately.


which mechanism of Donepezil cause that? I know Donepezil is Sigma 1 Agonist, and Sigma 1 increase glutaminergic system trafficking, can do it?
Or maybe Memantine doesn't have any "dissociative effects" and just "anticholinergic-delirium".(?)

 

[MiowCat]

bump~

 

[Xorkoth]

I know that memantine for sure has NMDA antagonism, so is a dissociative.

 

[grue]

Naturally it will do this. Memantine is a nicotinic acetylcholine receptor antagonist in addition to its action at NMDA and this is understood to be the source of the brain fog it produces for early users, not its NMDA antagonism, which is supposed to preserve normal NMDA neurotransmission within therapeutic dose ranges. Donepezil, as an acetylcholinesterase inhibitor, obviously increases both nicotinic and muscarinic acetylcholine activity.

The nACHrs rapidly sensitize and desensitize in the presence of a ligand. This is why given a stable blood level of memantine and some time, the brain fog disappears. Using donepezil to reverse the brain fog may be unwise, because uncontrolled muscarinic neurotransmission is toxic, and nicotinic and muscarinic acetylcholine compete to some extent. And indeed the combination has been shown to potentiate neurotoxicity in the rat brain:

https://www.ncbi.nlm.nih.gov/pubmed/17112636

A superior treatment for memantine brain fog when beginning the use of memantine or ramping up the dose, is nicotine. Lozenges, patch, gum.

 

[MiowCat]

Thanks for your replies.
--
We know Memantine doesn't any activity on PCP site ( in NMDA ) and can not induce dissociation like Phenylcyclidine and Ketamine.
people in "Erowid" and other sites say have dissociation trips with the big dose of Memantine but it's not true, 100 mg Memantine only induce delirium, not dissociation.
I am not sure if Memantine can induce Dissociation like ketamine or PCP.