Answer by José Francis:

I will complement the answer of Alexander van Hattem, that was very good.

First of all, the mechanism that you specify is impossible, because there aren’t reuptake proteins for acetylcholine. There are reuptakers for choline, and if you block them, you wouldn’t have the net effect of increase the time and concentration of acetylcholine on the synapse. As Alexander’s answer, we have colinesterase inhibitors, that results in higher acetylcholine actions.

Up to date, it is unknown if this kind of drugs can elicit dependence, but it is improbable because only drugs that acts or interfere in the reward system can do that. Thus, only drugs that imbalance dopamine can cause dependence. As you notice, methamphetamine can cause dependence, because this drug can increase the dopamine release in the brain.

You are right saying that the organism tries to come back to homeostasis, but in the case of taking a drug continuosly, it will be impossible to revert the process, so your organism will start to use other mechanisms to maitain homeostasis. For example, if you are increasing, artificially, a neurotransmitter, your brain will downregulate the receptors for it. This not always occur and depends on other factors, but I don’t know for sure if this occurs with acetylcholine. Nevertheless, it is highly improbable that imbalance in neurotransmitters results in neuronal death. Only if the concentration is maitained very high for prolonged periods of time, causing excitatory toxicity, and this is difficult to achieve even in people with chemical dependence. Most of the time, any damage caused by drugs in the brain can be reverted by just stop taking the drug.

I think my anwer plus Alexander’s ought to be enough. If you are thinking about nootropics in general, ask again, because nootropics can act by multiple mechanisms, like increase the blood flow to the brain in order to improve cognition, what had been resulting in clinical efficacy and it is currently used in patients that suffer from brain ischemia, for example.

Part 1 

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

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