How do typical and atypical antipsychotics differ in mechanism and side effects?

• A. Typical increase serotonin; atypicals increase dopamine
• B. Typical block D2 receptors with higher risk of EPS; atypicals block D2 and 5-HT2A with lower EPS but metabolic effects
• C. Typical block D2 and 5-HT2A; atypicals block NMDA receptors
• D. Typical have lower EPS; atypicals have higher EPS

Answer: (B)

The main idea is how receptor targets shape both how these drugs work and the side effects they produce. Typical antipsychotics act mainly as dopamine D2 receptor antagonists. Blocking D2 in the mesolimbic pathway helps lessen positive symptoms like hallucinations and delusions, but the same blockade in the nigrostriatal pathway leads to extrapyramidal symptoms—tremor, rigidity, dystonia, akathisia—because those motor pathways rely on dopamine signaling. They can also cause hyperprolactinemia by blocking dopamine’s inhibitory effect on prolactin release in the tuberoinfundibular tract.

Atypical antipsychotics share D2 antagonism but add strong blockade of serotonin 5-HT2A receptors. This serotonin blockade helps modulate dopamine release, reducing the risk of extrapyramidal symptoms and prolactin elevation compared with typicals. At the same time, their broader receptor effects, including interactions with other serotonin, histamine, and adrenergic receptors, contribute to metabolic side effects such as weight gain, glucose intolerance, and lipid abnormalities. So the distinction is D2-only blockade with higher EPS versus D2 plus 5-HT2A antagonism with lower EPS but more metabolic risk.