Clozapine's superior efficacy in treatment-resistant schizophrenia is best attributed to its relatively HIGH affinity for which receptor, compared to typical antipsychotics?

• A Dopamine D2 receptor
• B Muscarinic M1 receptor
• C Alpha-2 adrenergic receptor
• D 5-HT2A receptor (serotonin) ✓

Explanation

Clozapine's atypical profile stems from high 5-HT2A relative to D2 receptor affinity. The 5-HT2A blockade in cortical areas enhances prefrontal dopamine release, improving negative and cognitive symptoms while reducing D2-mediated extrapyramidal side effects. This serotonin-dopamine ratio hypothesis explains clozapine's efficacy in D2-refractory patients. Its muscarinic and histamine blockade account for side effects rather than efficacy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.