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Friday, 28 October 2011

Medications: What is Serotonin?

(This is part of a series of posts on the basics of psychopharmacology that I’m posting so that I can refer people back to it.  The first defined neurons, and the second described neuronal transmission.)

Serotonin is one of many chemicals in the human body that function as neurotransmitters – chemicals that allow individual neurons to communicate with one another.

In the early 20th century chemical transmission was hypothesized to be the method whereby neurons communicated with one another. This was demonstrated experimentally by Otto Loewi in 1921. The first neurotransmitter to be identified was acetylcholine.

Serotonin was discovered in 1935 by Vittorio Erspamer. He was looking at the contraction of cells in the intestinal system, and called the substance that seemed to produce the effect enteramine (for enteral, related to the intestines). In 1948 Maurice Rapport isolated the substance. He demonstrated that serotonin acted to increase the tension (or tone) in the tiny muscles governing the diameter of blood vessels. Blood is serum, thus the name became sero-tonin, the “blood vessel toner.”

Serotonin has subsequently been found to have many other effects as well, so its name is a result of the accident of discovery. It is also known by its chemical name, 5-hydroxytryptamine, or 5-HT.

For many years it was believed that serotonin was found exclusively in the peripheral nervous system (as opposed to the central nervous system, or CNS: the brain and spinal cord). This, like much else believed about it, was wrong.

About 95% of the body’s serotonin is found outside the central nervous system, mainly in the gastrointestinal tract.  About 5% is in the CNS.  This makes it a bit odd that almost every reference to serotonin in the popular press talks about its central (brain) effects.

The blood brain barrier

While we’re on the subject, let’s consider a common question: If people are thought to have problems due to serotonin deficits in the brain (more on this idea later), why don’t we just feed them extra serotonin?

The body is designed to protect the brain from infection, and to keep a relatively stable chemical soup for it to sit in. Consequently, the membranes separating the blood supply from the brain are somewhat more elaborate than those in the rest of the body.

This “blood-brain barrier” means that some chemicals, including drugs, that can reach the rest of the body are blocked from entering the central nervous system. Serotonin, oddly enough, is one of these. So if we fed a person large quantities of serotonin (a dangerous thing to do), the result would be no increase in brain levels.

Serotonin is manufactured within the body (and within the central nervous system) from other substances, some of which are in the diet. These chemicals, being earlier in the set of steps that eventually lead to serotonin, are termed precursors. Precursors for serotonin include substances such as tryptophan and s-adenosylmethionine (or SAM-e). Some precursors, like those just mentioned, can cross the blood-brain barrier, and so can be absorbed from the diet.

So why bother with the various drugs designed to help brain-based serotonin systems? Why not just dose up on precursors, which would result in more serotonin?

This seems like a sensible idea, but there are some problems with it.

For example, the precursor we choose may not be the limiting factor in the production of serotonin. Imagine that in order to create a serotonin molecule we need equal parts of Substance A and Substance B. We decide to provide supplements of Substance A. But, unbeknownst to us, the person already has an ample supply of Substance A. They lack Substance B. We can give them as much Substance A as they can stand, and it won’t make any difference to the amount of serotonin they produce.

This seems obvious, but in practice the process of neurotransmitter manufacture is sufficiently complicated that precursor supplementation is extremely tricky.

Tricky or not, another option is to do it anyway and just see what happens. (Of course, many substances are toxic at high doses, so we have to be somewhat cautious about this.) The result is that attempts to raise brain serotonin levels – and resolve problems thought to be related to serotonin deficiency – with supplementation just haven’t tended to work out well.

Next:  What is the monoamine hypothesis?

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