Atypical antipsychotics, also known as second-generation antipsychotics, are characterized by their combined serotonin 5-HT2A receptor antagonism and D2 receptor antagonism. The 5-HT2A antagonism is thought to modulate the D2 blockade, particularly in the nigrostriatal pathway, thereby reducing the risk of extrapyramidal symptoms (EPS) compared to typical (first-generation) antipsychotics, which primarily block D2 receptors. Stronger D2 blockade (A) would increase EPS. D1 affinity (B) is not the primary differentiating factor for EPS. Selective blockade of D2 receptors in the nigrostriatal pathway (D) would cause EPS, not reduce it.
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