This chapter is a comprehensive account of the medicinal chemistry of the
antidepressant drugs. It provides the mechanism of drug action and details of the
structure-activity relationships (SAR) of the antidepressant and related drugs to give
the knowledge base for pharmacists. After a study of this chapter, students will be able
to:
• Relate principles of affective disorders including the biogenic amine hypothesis and
depression.
• Describe the roles of dopamine, serotonin and norepinephrine in depression and how
these roles relate to the mechanism of action of antidepressant drugs.
• Describe different classes of antidepressant drugs with examples.
• Compare the chemical structures of all the classes of antidepressant drugs and relate
their action with structures.
• Illustrate the mechanism of action, SAR, metabolites, and clinical considerations of:
▪ Serotonin and norepinephrine reuptake inhibitors
o Tricyclic antidepressants (TCAs)
o Phenylalkylamines
▪ Selective serotonin reuptake inhibitors (SSRIs)
o Phenoxyphenylalkyl amines
o Phenylalkylamine
▪ Monoamine oxidase inhibitors (MAOIs)
▪ Miscellaneous antidepressant drugs
Keywords: Antidepressant drugs, Clinical use of antidepressant Drugs, Drug
receptor interaction, Major Depressive Disorder (MDD), Selective
Norepinephrine Reuptake Inhibitors (NRIs), Serotonin and Norepinephrine
Reuptake Inhibitors (SNRIs) Selective Serotonin Reuptake Inhibitors (SSRIs),
Structure-Activity Relationship (SAR).
