SSRIs work by increasing the amount of serotonin in your brain. But they can also have side effects like constipation (the internet says SSRIs block acetylcholine?), and you can’t take NSAIDs too because of a risk of stomach bleeding. How do SSRIs do those things if they are focused on serotonin? Does acetylcholine use the same receptors as serotonin? I’m also interested in how they cause other side effects.
In: Biology
To understand the side effects, I think it would be a good idea to look at the role of serotonin in the body. Although it’s a neurotransmitter and typically thought of as being found in the nervous system, serotonin is mostly found in the digestive system and helps control bowel movements. Also, it is tricyclic antidepressants that block acetylcholine transporters, not so much the newer SSRIs. So to my understanding, SSRIs wouldn’t really cause constipation, a serotonin shortage in the gut apparently reduces the number of neurons in the gut, leads to a deterioration of the gut’s lining, and slows the movement of contents through the GI tract. So…decreased levels of serotonin, it seems like, would cause constipation, not excess.
Constipation since serotonine is involved intenstinal motility. Most of the serotonine in our bodies is used in the intestines.
Platelets are cell fragments that circulate the blood and is important for blood clotting. A blod clot is made of activated platelets and a sticky gluey protein called fibrin holding the platelets together.
SSRIs increase bleeding risk by inhibiting serotonin uptake in platelets. The platelets secrete serotonine when activated and this causes further platelets to be activated. Interfering with increase bleeding risk.
NSAIDs also inhibits platelet activation but through another mechanism (inhibiting tromboxane A2). Therefore these drugs should not be used together.
Your gut has a secondary nervous system that controls the movement of food. The neurons of that system work in more or less the same way as the ones in your brain do, so things that change how neurotransmitters like serotonin work generally affect both (although the goal in drug development is usually to find substances that focus specifically on what you’re trying to change).
I think a common misconception of drugs in general is that they only end up in the tissue they are meant to be in, for example antidepressants in the brain. In reality, when you take a pill that compound ends up pretty much everywhere throughout the entire body. Most drug side effects arise from activity in tissues other than the target one (liver, heart, intestines, etc.)
There is some research ongoing into targeted delivery systems, but with a plain old small molecule like an SSRI this is an insurmountable problem.
Going just a bit deeper, pharmacological effects result from the binding of a drug molecule to its intended target in the body. And the drug doesn’t know where it is going, it is just bouncing around the body randomly until it finds something it has high affinity to, then it sticks around for a while. Modern medicinal chemistry has gotten fairly good at manipulating chemical structure to build in selectivity (given a lot of time and resources) but designing something that only binds to one of the countless proteins, enzymes, receptors, etc. in the human body is a tall order.
Thanks all, this is very interesting!
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