Advancements in antipsychotic pharmacology

Abstract

This thesis examines how antipsychotic medications have evolved from simply blocking dopamine receptors to precisely balancing brain pathways. First- and second-generation antipsychotics treat psychosis by blocking dopamine D2 receptors, but their clinical use is limited by severe side effects. First-generation drugs cause movement disorders like extrapyramidal symptoms, while second-generation drugs cause weight gain and diabetes by blocking off-target histamine H1 and muscarinic M3 receptors. Third-generation drugs improve on this by acting as partial agonists; they balance dopamine levels, treating psychosis while protecting normal movement control in the basal ganglia. The newest class of medications avoids dopamine receptors completely, instead targeting muscarinic M4 and TAAR1 receptors to lower dopamine release at the presynaptic level, which eliminates the risk of movement side effects. Ultimately, combining these new receptor targets with genetic testing for CYP2D6 liver enzymes allows doctors to personalize drug dosing, making schizophrenia treatment both safer and more effective.