Answer by Alexander van Hattem:

I’ll be the first to admit that I am not an expert in nootropics, but since I was asked to answer and there are no other replies yet, I’ll have a go.

Nootropics” is a very vague term, not a single class of drug.  It can refer to any substance that is used with the intent of improving cognitive function.  I’m not sure if your question is based one the assumption that they all work in the same way (they don’t), or if you are asking specifically about ones which have the mechanism of action you specify (which I think must be the case based on the question details).

To my knowledge, there aren’t technically any drugs that works as acetylcholine reuptake inhibitors, or “prevent the re-uptake of acetycholine”.  Instead, there are a few drugs that work as cholinesterase inhibitors.  Cholinesterase is the enzyme that breaks down acetylcholine, so inhibiting it does increase the amount of acetylcholine remaining in the system, but it is not the same process by which reuptake inhibitors like SSRIs work.

Most of the evidence concerning the use of cholinesterase inhibitors is in patients with Alzheimer’s Disease and other kinds of dementia, where they have indeed to be shown to slow the decline in memory and cognitive function, though they generally do not reverse impairment that has already occurred, or stop the disease process altogether.

I think the use of cholinesterase inhibitors in people without dementia is based on the idea that if it helps a damaged brain, it must also help a healthy brain, but that is not a logical connection to make.

As for safety, most side effects are dose-dependent, so at low doses should be non-existent or manageable.  Their actions on the parasympathetic nervous system can cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure, as well as the delightfully named SLUDGE syndrome.

Part 2

How do nootropics, that prevent the re-uptake of acetyl-choline, work?