A patient develops sudden-onset fever, muscle rigidity, altered consciousness, and autonomic instability 48 hours after starting a high-potency antipsychotic. The pathophysiological mechanism of this syndrome involves:

• A Excessive 5-HT1A stimulation in the brainstem raphe nucleus causing central hyperthermia
• B Alpha-1 adrenoceptor blockade causing peripheral vasodilation and compensatory heat conservation
• C Muscarinic M2 receptor activation in cardiac muscle causing autonomic instability
• D Abrupt D2 receptor blockade in the hypothalamus and striatum, disrupting dopaminergic thermoregulation and causing skeletal muscle hypermetabolism ✓

Explanation

Neuroleptic Malignant Syndrome (NMS) results from rapid or extensive D2 receptor blockade — in the hypothalamus causing hyperthermia, in the nigrostriatal pathway causing rigidity, and in the mesocortical pathway causing altered consciousness. The resulting skeletal muscle hyperactivity generates massive heat. Key differentiator from serotonin syndrome: NMS has 'lead-pipe' rigidity, slow onset, no clonus, and no diarrhoea.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.