Final answer:
The MOA of TCAs is related to its ability to inhibit the reuptake of monoamines like serotonin and norepinephrine, increasing their levels in the synaptic cleft.
Step-by-step explanation:
Tricyclic Antidepressants Mechanism of Action
The mechanism of action (MOA) of Tricyclic Antidepressants (TCAs) is primarily related to their ability to inhibit the reuptake of monoamines, such as serotonin (5-HT) and norepinephrine, into the presynaptic neuron. By blocking this reuptake, TCAs increase the levels of these neurotransmitters in the synaptic cleft, which enhances neurotransmission and alleviates the symptoms of depression. Additionally, TCAs have a structure that prevents the conjugation of the rings, distinguishing them from chemically similar phenothiazines and resulting in different pharmacological effects.
TCAs, like imipramine and amitriptyline, effectively treat major depression by increasing the levels of serotonin and norepinephrine. However, they may cause sleepiness and a feeling of unhappiness or increased anxiety in normal subjects, but over time they elevate mood in depressed patients. This outcome contrasts with the effects seen in drugs like monoamine oxidase inhibitors (MAOIs), which can have a stimulating effect on mood even when administered to non-depressed individuals.
Furthermore, TCAs do not act as agonists of the neurotransmitters; they do not mimic neurotransmitter binding to the receptor, nor do they act by promoting the synthesis of neurotransmitters. Instead, TCAs are considered antagonists, though their primary action is to inhibit the reuptake mechanism, leading to an increase in neurotransmitter levels and subsequent improvement in depressive symptoms.