Pharmacology · Antiepileptics and CNS Drugs (Antipsychotics, Antidepressants, Sedatives)

Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia. Its unique receptor profile compared with typical antipsychotics includes:

  • A Low D2 receptor occupancy (<60%), high 5-HT2A, D4, muscarinic M1, H1, and alpha-1 antagonism
  • B High D2 receptor occupancy (>80%) with minimal serotonin 5-HT2A antagonism
  • C Selective D3/D4 antagonism with no effect on 5-HT, muscarinic, or histamine receptors
  • D Partial agonism at D2 and D3 receptors with 5-HT1A partial agonism
Correct answer: A. Low D2 receptor occupancy (<60%), high 5-HT2A, D4, muscarinic M1, H1, and alpha-1 antagonism

Explanation

Clozapine has low D2 receptor occupancy (~40–60%), rapid D2 dissociation, and potent antagonism at 5-HT2A, D4, muscarinic M1/M4, H1, and alpha-1 adrenoceptors. This multi-receptor profile underlies its efficacy in treatment-resistant cases and negative symptoms while minimising EPS. Aripiprazole (not clozapine) is the D2/D3 partial agonist.

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

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