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Tricyclic antidepressant

Tricyclic Antidepressant effect of these drugs depends on their effect on biogenic amine neurotransmitters:

1. Imipramine, clomipramine, amitriptyline and doxepin are Tricyclic Antidepressant. They block the amines norepinephrine (NE) or serotonin reuptake pumps and permit a longer sojourn of neurotransmitter at the receptor site. They also bind to c— adrenergic, histaminergic (H1) and cholinergic receptors (responsible for many of the side effects). Desipramine and nortriptyline are also .Tricyclic Antidepressant. They act predominantly inhibiting norepinephrine reuptake.

2. Amoxapine and maprotiline are tetracyclic Antidepressants and not Tricyclic Antidepressant. They also act by inhibiting NE reuptake leading to increased concentration of NE in the synaptic cleft in the central nervous system

3. Some of the second generation tricyclic Antidepressants such as trazodone, nefazodone, and mirtazapine mainly act by antagonizing subtypes of serotonin receptors (5-HT2A or 5-HT2C). Mirtazapine also causes antagonism of cr2— adrenergic receptors; bupropion alters the output of norepinephrine. Thus newest Antidepressants of this group act through serotonergic and nor-adrenergic effects.

4. Monoamine oxidase inhibitors act by blocking a major degradative pathway for the amine neurotransmitters. So they permit more amines to accumulate in presynaptic stores and more to be released.

5. Recently selective serotonin re uptake inhibitors (SSRIs) such as sertraline, fluoxetine, fluvoxamine, paroxetine and citalopram have been developed. These Antidepressants drugs have minimal autonomic toxicity. They act selectively by blocking serotonin reuptake and increasing the levels of serotonin in the synaptic cleft.

B. Receptor and post-receptor effects:

1. There occurs decrease in norepinephrine stimulated cAMP. Beta-adrenoceptor binding is also decreased by selective norepinephrine uptake inhibitors, those with mixed action on norepinephrine, serotonin, monoamine oxidase inhibitors and even electroconvulsive therapy. Such changes do not consistently occur after selective serotonin uptake inhibitors, a2 receptor antagonists and mixed serotonin antagonists.

2. It is suggested that enhanced stimulation or responsiveness of post-synaptic 5-HT1A receptors are particularly important in the action of tricyclic Antidepressants.

3. It is possible that Antidepressants effect of these drugs may be due to long-term intracellular changes which involve phosphorylation of various regulating elements including those within the nucleus.

4. It is suggested that enhanced serotonin throughput is necessary for the Antidepressants action of serotonin but not for norepinephrine uptake inhibitors while enhanced norepinephrine throughput is needed of norepinephrine uptake inhibitors.

Tricyclic Antidepressant: Imipramine is a dibenzazepine derivative and is commonly used tricyclic Antidepressants drug. So it is discussed as a prototype.

About Dr. Muna

Dr. Muna Taqi is a Dental surgeon from India who has more than 10 years of experience in the field of Oral & Maxillofacial surgery, Endodontics, & Pedodontics. She has worked in multinational medical corporates in Middle East and is also a consultant dental surgeon for many. She has authored many articles for medical journals & websites and is a consultant dental expert for Healthdrip.

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