You may have heard about the “imbalance of chemicals in the brain” leading to “mental illness.”

We are going to make our best effort in explaining this..  The research has been difficult considering the abundance of conflicting information.  So I will summarize what we found..

These chemicals are called neurotransmitters (chemicals aka messengers).

Neurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of the synapse.

There are many different ways to classify neurotransmitters.
Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.

Primary Neurotransmitters:

▪ Amino Acids: glutamate, aspartate, serine, γ-aminobutyric acid (GABA), glycine

– dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline) [also known Catacholamines]
– serotonin (SE, 5-HT), melatonin
– histamine

▪ Others: acetylcholine (ACh), adenosine, anandamide, nitric oxide, etc.

Neurotransmitter Systems:

DOPAMINE: EFFECTS motor system, reward system, cognition, endocrine, nausea

SEROTONIN: EFFECTS increase (introversion), mood, satiety, body temperature and sleep

NORADRENALINE: EFFECTS reward system, arousal

CHOLINERGIC: EFFECTS learning, short-term memory, reward, arousal

1. Specific transporter proteins called monoamine transporters exist, that transport monoamines in or out of a cell.

These are the dopamine transporter (DAT), serotonin transporter (SERT), & norepinephrine transporter (NET) in the outer cell membrane. & the vesicular monoamine transporter (VMAT1 and VMAT2) in the membrane of intracellular vesicles.

2. After release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal.

3. There, they can be repackaged into synaptic vesicles OR degraded by the enzyme, monoamine oxidase (MAO).

note:  Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines.
There are also Catechol O-methyl transferase (COMT) one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine.  MAO’s and COMT’s are located in the presynaptic neuron and in the synaptic cleft.

In humans there are two types of MAO: MAO-A and MAO-B.

MAO-A is particularly important in the catabolism of monoamines ingested in food.

Both MAOs are also vital to the inactivation of monoaminergic neurotransmitters, for which they display different specificities.

▪ Serotonin, melatonin, norepinephrine, and epinephrine are mainly broken down by MAO-A.

▪ Phenethylamine is mainly broken down by MAO-B.

▪ Both forms break down dopamine equally.

Examples of Antidepressants (a few among many):

monoamine oxidase inhibitors (MAOIs) – The first antidepressant created and now reserved as the last line in defense used ONLY when the other classes of antidepressant drugs have failed. JOB is to stop the MAO’s from taking (breaking down) the monoamines.  This medicine can permanently or temporarily disable the MAO.  MAOI’s are each designed to target MAO-A or MAO-B, or both, or more of one over the other.

selective serotonin reuptake inhibitors (SSRIs) – JOB is to stop the reuptake of serotonin (by blocking the transporter, delay its ability to take it). There needs to be a certain amount of serotonin (or any of the individual monoamines) in order for it to produce its effect. Remember, when it goes into reuptake, its effect will cease.  So stopping the reuptake for a while, will allow serotonin to increase in numbers in that area (bottle neck) and produce its effect.  This is temporarily correcting the imbalance, the deficit of serotonin.  Serotonin effects mood, hunger (the inability to eat after a meal), sleep, body temp, reduces sense of pain, etc.

serotonin-norepinephrine reuptake inhibitors (SNRIs) – JOB is the stop the reuptake of serotonin AND norepinephrine. Norepinephrine effects arousal and reward system.  Reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects..Rewards induce learning, approach behavior and feelings of positive emotions.

tricyclic antidepressants (TCAs) – JOB is to stop the reuptake of serotonin and norepinephrine. In addition, an affinity for Antagonists and Agonists.  An agonist is a chemical that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.
An agonist produces an action. An antagonist blocks an action of an agonist.  Example, it may block histamine, therefore this medicine can also act like an antihistamine.


5-HT (5-hydroxytryptamine) is Serotonin.  It is biochemically derived from Tryptophan.  Above image is the normal workings of nerve communication.
Below image shows how an SSRI blocks the reuptake transporter.


Images from Sources:

Quoted and Paraphrased from Sources:

  • lizanka

    I’,m a doctor in Brasil. Endocrinoligist.And you. What organization is? Any University?

    May 9, 2012 at 4:30 am
  • KnowMental

    Hi Lizanka, I set up this blog to share information/articles I find about mental disorders and the advice I receive in Therapy. Learn more: I set up the organization, KnowMental LLC to launch a sister project:

    May 10, 2012 at 10:13 pm

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