A patient on clozapine for treatment-resistant schizophrenia develops fever, agranulocytosis, and drooling. The receptor most responsible for the drooling (sialorrhea) as an adverse effect of clozapine is:

• A Muscarinic M4 receptor antagonism reducing salivary flow
• B Paradoxical muscarinic M1 agonism at salivary glands ✓
• C Alpha-2 adrenergic receptor antagonism increasing salivary gland sympathetic tone
• D 5-HT2A receptor antagonism causing reflex salivation

Explanation

Clozapine is unique among antipsychotics in causing sialorrhea (excessive salivation) rather than the xerostomia seen with other anticholinergic antipsychotics. This paradox arises because clozapine, despite weak overall muscarinic antagonism, acts as a partial agonist at M1/M4 receptors in salivary glands, directly stimulating saliva secretion. This explains why anticholinergic agents like hyoscine or glycopyrrolate can paradoxically reduce clozapine-induced drooling.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.