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Mental disorders
Depression and Manic Depression
Anxiety Disorders
Alzheimer’s-type Dementia

Help Lien : Neurobiology of Depression Lien : G protein (animation) Lien : 5-HT receptor
Lien : The role of noradrenaline in depression: a review. Lien : Noradrenergic approaches to antidepressant therapy.

Receptors that are paired with G-proteins, such as 5-HT1 and 5-HT2 receptors, have a relatively slow reaction time because of the intermediaries involved. Also, the signal does not trigger an action potential directly, but instead alters the probability that one will be triggered. In such cases, the serotonin is said to act as a neuromodulator.

In contrast, in a 5-HT3 receptor, the ion channel opens almost instantly, and the serotonin directly transmits a signal that can trigger the propagation of a new action potential. In this case, the serotonin acts as a neurotransmitter (or neuromediator).


Two of the nine serotonergic nuclei in the brainstem, the dorsal and medial raphe nuclei, are composed of neurons whose fibres terminate in many different areas of the brain, such as the forebrain and the limbic system. The fibres arising from the dorsal and medial raphe nuclei represent almost the only source of serotonin in the anterior portions of the central nervous system.

There are 15 known types of serotonin receptors (also known as 5-HT receptors, after the chemical name for serotonin, 5-hydroxytryptamine). These 15 types can be grouped into 3 major families according to their mode of operation. Click on each of the 3 buttons below to see how each of these 3 families of receptors operates.

Serotonin is clearly not the only neurotransmitter involved in depression. For example, there are known, close linkages between the serotonergic system and the norepinephrinergic system in the central nervous system. Thus norepinephrine, which is affected by several antidepressants, also is involved in depression.

Many studies have also shown that the activation of the body's stress axis has a significant effect on depression. Depressed or suicidal patients show signs of hypersecretion of stress hormones, in particular glucocorticoids from the adrenal glands, which affects their serotonergic systems.

Several other serotonin receptors have been identified (5-HT4, 5-HT5, 5-HT6, 5-HT7). For the most part, they work like 5-HT1 and 5-HT2 receptors: with a G protein that modifies an ion channel or a membrane enzyme.

Since roughly the 1970s, neurotransmitters and their receptors have been the main focus of research on mental disorders. But with the discovery of increasingly complex biochemical cascades within the cell, scientists are increasingly realizing that fluctuations in neurotransmitters such as serotonin may be only the tip of the iceberg, and that to understand complex phenomena such as depression, they will need to examine in detail what happens inside a neuron once a neurotransmitter has bound to its receptor.


Lien : Antidépresseurs Lien : Les antidepressants Lien : Treating depression Lien : Dépression génétique
Lien : Les antidepressants Lien : Link Found Between Serotonin Transporter Gene And BPAD Lien : The range and properties of medicines for depression Lien: Brain noradrenaline and the mechanisms of action of antidepressant drugs.
Histoire : The making of a miracle cure? - The history of prozac.

Monoamine molecules are slightly larger than amino acid molecules and form a very large class of neurotransmitters that includes dopamine, epinephrine, norepinephrine, and serotonin. Monoamines are divided into two sub-classes: catecholamines (dopamine, epinephrine, and norepinephrine) and indoleamines (serotonin).

The involvement of monoamines in depression was discovered in the 1950s. Early in that decade, some physicians noticed that nearly 15% of the patients who were taking reserpine as a treatment for hypertension had fallen into a deep depression. It was then discovered that the reserpine was breaking down the catecholamines in the patients' brains.

At just about the same time, the opposite observation was made for another medication: a molecule that was being prescribed as a treatment for tuberculosis was improving the mood of certain depressed patients. A more extensive analysis of this molecule revealed that it inhibited the normal degradation of monoamines by the enzyme monoamine oxidase (MAO). The researchers inferred that this beneficial effect on the patients' depression was attributable to higher levels of monoamines' being active in the synapses of their brains. This insight quickly led to the development of monoamine oxidase inhibitors (MAOIs), the first generation of antidepressants.

Lien : Catecholamines Lien : LES CATÉCHOLAMINES Lien : LA SEROTONINE Lien : Indoleamines:  The Role of Serotonin in Clinical Disorders

Many different molecules are now regarded as antidepressants. Each of these molecules increases the amount of certain specific neurotransmitters in certain specific regions of the brain.

Over the years, as scientists have demonstrated the involvement of additional neurotransmitters in depression, they have established a classification of antidepressants according to their molecular structure and mode of action. Antidepressants are now classified into three main families: monoamine oxidase inhibitors (MAOIs), tricyclics, and selective serotonin reuptake inhibitors (SSRIs).

There are also a number of new medications that act through unique mechanisms and are therefore known as atypical antidepressants. Though they have no action mechanisms in common, all of these atypical antidepressants increase the level of certain neurotransmitters in the synapses.

Lastly, a mood-stabilizing medication such as lithium plays a distinctive role in the treatments available for bipolar disorder, both because of its effectiveness and because it consists of a single chemical element.

Click on each link below to learn more about the mode of action and effects of each type of antidepressant medication.

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) were among the first antidepressants to be developed. To understand how these molecules act on depression, you must first know that monoamines are neurotransmitters, such as serotonin and norepinephrine, that are involved in mood control, among their other functions (see sidebar).

Normally, these neurotransmitters are metabolized by an enzyme called monoamine oxidase. But monoamine oxidase inhibitors, as their name implies, block this enzyme, thus allowing larger amounts of serotonin and norepinephrine to remain available.

Nowadays, MAOIs are used less often as front-line antidepressants, because of their side effects and the dangers involved in combining them with other medications. Also, people who are taking MAOIs must severely limit their intake of foods that are rich in tyramine, because MAOIs inhibit the breakdown of tyramine just as they do that of monoamines, and if too much unmetabolized tyramine builds up, it can lead to high blood pressure.

Phenelzine (Nardil) and tranylcypromine (Parnate) are examples of MAOIs.

Linked Module : Monoamine Oxidase Linked Module : Monoamine Oxidase Inhibitors

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