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This article throws light upon the two main types of drugs used as antidepressants and mood elevators. They are: 1. Monoamine Oxidase (MAO) Inhibitors 2. Tricyclic and Related Drugs.
Type # 1. Monoamine Oxidase (MAO) Inhibitors:
MAO is a mitochondrial enzyme and involved in oxidative deamination of biogenic amines (adrenaline, noradrenaline, dopamine, 5-hydroxytryptamine). Two isozyme forms of MAO have been identified depending on the distribution and deamination reactions.
MAO-A:
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It is located in the peripheral adrenergic neurons, intestinal mucosa and human placenta and it preferentially deaminates 5HT. Inhibitors of this isozyme are clorgiline, moclobemide.
MAO-B:
It is predominantly located in certain areas of brain and platelets. It preferentially deaminates phenyl-ethyl-amines. The selective inhibitor of this isozyme is selegiline. However, liver contains both the isozymes of MAO.
MAO inhibitors noncompetitively and irreversibly inhibit MAO and thus allow the accumulation of NA, dopamine and 5HT in their respective neurons in the brain and periphery. Only MAO-A inhibitors possess antidepressant property. MAO-B inhibitors are not effective in depression.
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MAO inhibitors are rarely used now because of the following reasons:
1. Marked toxicity, particularly hepatotoxicity;
2. Serious and fatal interactions with drugs and food; and
3. Compared to tricyclic antidepressants, their potency is very low.
Type # 2. Tricyclic and Related Compounds:
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Tricyclic Compounds:
Imipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, doxepine.
Tetracyclic Compounds:
Mianserin, amoxapine, maprotiline, desipramine.
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Atypical Compounds:
Trazodone, fluoxetine, bupropion, nefazodone.
Mechanism of Action:
These inhibit the active uptake of biogenic amines NA, 5-HT, dopamine etc. into their respective neurons.
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Selective Inhibitors of NA Uptake:
Desipramine, maprotiline, amoxapine.
Selective Inhibitors of 5-HT Uptake:
Doxepine, trazodon, fluoxetine.
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Mixed Inhibitors of NA and 5-HT:
Imipramine, amitriptyline, clomipramine, however, nortriptyline and dothiepin have more marked effect on NA uptake.
In addition to the above, certain second generation antidepressants are also available-e.g. doxepin, clomipramine, mianserin, amoxapine, fluoxetine and maprotiline.
