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Older chance-discovery drugs have many clinical effects either because they affect a site of action with broad implications for organ function or because they affect multiple sites of action.
The brain communicates with itself through the use of special chemicals called neurotransmitters such as serotonin, norepinephrine, and dopamine.There are many different types of antidepressants available today.The two most valuable classes are Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs).Tricyclic antidepressants were discovered by chance. The TCAs were the result of an unsuccessful attempt to improve on the antipsychotic effectiveness of phenothiazines (medication used in the treatment of schizophrenia).Molecular modifications of phenothiazines led to synthesis of imipramine, the first clinically useful tricyclic antidepressant.Both SSRIs and TCAs work by prolonging the effects of neurotransmitters, but have different mechanism of action.Tricyclic antidepressants work by raising the levels of neurotransmitters serotonin and norepinephrine in the brain by slowing the rate of reuptake (reabsorption) by nerve cells.Unlike TCAs antidepressants, SSRIs are highly selective: they act as weak inhibitors in the reuptake of non-serotonergic neurotransmitters such as norepinephrine, but act as strong inhibitors in the reuptake of serotonin.Because of this selectivity, there are fewer side effects associated with SSRIs than with TCAs and their side effects are due to actions at other serotonin receptors in the central nervous system and the gut wall.Tricyclic antidepressants are a class of antidepressant drugs first used in the 1950s.They are named after the drugs' molecular structure, which contains three rings of atoms.