A 60-year-old man with diabetic gastroparesis developed parkinsonian tremor while on metoclopramide. His physician switches him to domperidone. What property of domperidone accounts for its lower risk of extrapyramidal symptoms?

• A It is a dopamine receptor agonist rather than an antagonist
• B Selective activity at 5-HT4 receptors only
• C Poor penetration across the blood-brain barrier ✓
• D Rapid hepatic glucuronidation to inactive metabolites

Explanation

Both drugs block peripheral dopamine D2 receptors in the chemoreceptor trigger zone and gut wall to produce prokinetic and antiemetic effects. Metoclopramide crosses the blood-brain barrier and centrally blocks D2 receptors in the basal ganglia, causing dystonia, parkinsonism and tardive dyskinesia. Domperidone is largely excluded from the brain by efflux transport and poor permeability, so central dopaminergic effects are minimal.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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