Monoamine oxidase inhibitors

Monoamine oxidase inhibitors, or MAOIs, are a class of medications used in the treatment of depression, which is a mood disorder that causes a persistent feeling of sadness and loss of interest in everyday activities.

Even though the exact cause of depression is still unknown, there is some evidence that suggests it’s related to low levels of serotonin, norepinephrine, and dopamine, which are also called monoamines because they have only one amine group.

Now, monoamine oxidase inhibitors work by increasing levels of serotonin, norepinephrine, and dopamine, which helps to alleviate the symptoms of depression.

Alright, now within the brain, there are many different types of neurons, but we’re going to focus only on three: serotonergic neurons that release serotonin, noradrenergic neurons that release norepinephrine, and dopaminergic neurons that release dopamine.

Each of these neurons synthesizes and stores neurotransmitters in small vesicles, so when an action potential reaches the presynaptic membrane, these vesicles fuse with the membrane, releasing neurotransmitters in the synaptic cleft.

Serotonergic neurons release serotonin, which then binds to 5-HT2 receptors, thereby increasing neural stimulation and regulating mood, feeding, and reproductive behavior.

On the other hand, noradrenergic neurons release norepinephrine, which hooks up to norepinephrine receptors (NE receptors), boosting alertness and focus.

Lastly, dopaminergic neurons release dopamine, which binds to dopamine receptors, stimulating cognitive functions, motivation, and awakeness.

As long as there’s a high enough concentration of neurotransmitters in the synaptic cleft, the postsynaptic neurons will continue to fire.

Now, each of these presynaptic neurons has small reuptake proteins, which pump the neurotransmitters from the synaptic cleft back into presynaptic neurons.

Once inside the neuron, a class of enzymes called monoamine oxidases will break down some of these neurotransmitters; monoamine oxidase A breaks down serotonin, norepinephrine, and dopamine; and monoamine oxidase B only breaks down dopamine.

The neurotransmitters that are not broken down are packaged into pre-existing vesicles, waiting to be released once more.

Now, in people with major depressive disorder, MAOIs are used to increase the levels of all the neurotransmitters related to depression.

It’s important to note that MAOI are not the first-line therapy due to their severe side effects.

Instead, selective serotonin reuptake inhibitors, or SSRIs, are used as the first-line therapy.

MAOIs can be used as the second or third line therapy, and they are especially effective in treating atypical depression.

In contrast to major depressive disorder, which is characterized by a persistent feeling of sadness, individuals with symptoms associated with atypical depression are able to improve their mood in response to positive events and circumstances.

They also experience increased appetite, weight gain, sleepiness, and fatigue.

Now, MAOIs are subdivided into two types: non-selective and selective.

Non-selective MAOIs, such as isocarboxazid, phenelzine, and tranylcypromine inhibit monoamine oxidase A and monoamine oxidase B, so serotonin, norepinephrine, and dopamine levels will increase.

These medications are also called irreversible MAOIs because they bind irreversibly to the enzymes, permanently blocking their function.

Once these enzymes are inhibited, the monoamines neurotransmitters get packed into pre-existing vesicles.

So, the next time an action potential reaches the presynaptic membrane, more neurotransmitters are released into the synaptic cleft and thus alleviating the symptoms of depression.

On the other hand, selective MAO-B inhibitor like selegiline and rasagiline will only inhibit MAO B, so they only increase the level of dopamine.