I’ve been on a ‘mechanism of action’ kick lately, stressing the importance of understanding how exactly substances that you’re taking influence the body in order to have their desired effect. To do this, you need a fundamental understanding of the system the system you’re manipulating. When it comes to nootropics or any substance that has some behavioral or cognitive effect, this is usually the result of altering some part of a neurotransmitter system. Therefore, to understand how these substances work you need a basic knowledge of the neurotransmitter lifecycle.
What is the neurotransmitter lifecycle?
This is the process that all neurotransmitters go through from synthesis to removal from the synapse. The steps are:
-Synthesis from precursor
-Packaging into vesicles
-Release
-Action on receptors
-Clearance from the synapse (enzymatic breakdown or reuptake transporter)
Neurotransmitters are synthesized from precursors in the synaptic terminal by at least one enzyme, packaged into vesicles by a transporter, released into the synapse, bind to and activate receptors, and are then cleared from the synapse by enzyme or reuptake to terminate the signal. All of these steps can be targeted by drugs/nootropics in order to produce their effect, though nootropics typically only target a select few stages. To my knowledge there aren’t any that inhibit vesicular packaging, whereas there are pharmaceutical drugs that do.
Nootropics tend to act on either synthesis, receptors, or the two ways of clearance from the synapse, generally in an effort to increase signaling of a desired neurotransmitter system. In order to so that you can increase synthesis, positively modulate receptors/activate them directly, and inhibit synaptic clearance.
This is where it gets a bit tricky because you need to know your enzymes. Inhibiting tyrosine hydroxylase is going to have a wildly different effect to inhibiting monoamine oxidase. The former will decrease dopamine synthesis, while the other increases signaling of the monoamines. Thankfully, its easy enough to look this stuff up at a moments notice, but its important to know that inhibiting an enzyme has varying effects based on the enzyme’s function.
Increasing synthesis can be as simple as providing an increase in neurotransmitter precursor, or involve upregulating the synthesis enzymes themself (like bromantane with tyrosine hydroxylase). In either case, you’ll end up producing more neurotransmitter than can be released into the synapse.
Positively modulating receptors is quite simple, it just means the compound binds to the receptor and alter its shape. This change in shape causes the receptor to either become more sensitive to endogenous neurotransmitter or have a more pronounced response when it binds. There is also the change that a compound is a direct agonist or antagonist at a receptor. It’s less frequently seen in nootropics, but it can happen.
Clearance from the synapse is a frequently affected mechanism of action, usually the inhibition of an enzyme or reuptake transporter. The end result is more neurotransmitter in the synapse for longer so that it can act on receptors more. It enhances signals by preventing their termination. All neurotransmitters have some enzyme that breaks them down in the synapse (i.e. GABA transaminase, Monoamine Oxidase, Acetylcholinesterase), but only most have a dedicated transporter (acetylcholine does not).
Once you have a basic understanding of this lifecycle and how neurons work generally, understanding mechanisms becomes quite simple with access to google.
“Oh, this inhibits acetylcholinesterase”
*googles what’s acetylcholinesterase*
“Okay, it breaks down acetylcholine, so it must increase its signaling by inhibiting its breakdown.”
That’s how I see it at least, though it may be different based on your level of knowledge. I’d like to believe it's fairly easy to get to that point if you care enough to, and you should want to get to that point if you are on the lookout for brain-enhancing supplements.
Anyway, this *hopefully* shed some light into how nootropics or even pharmaceutical drugs produce their desired effects, as well as taught you a little about the neurotransmitter lifecycle. Remember: It’s crucial to understand it if you want a deeper understanding of how these compounds work and may interact with one another.
Thank you for reading!