Methylnaltrexone is used to treat opioid-induced constipation without reversing analgesia. This selectivity is due to:

• A Selective antagonism of mu receptors in the colon only, due to local administration
• B Partial agonism at kappa receptors in the gut, countering mu-mediated constipation
• C Selective antagonism of peripheral mu receptors with no CNS antagonism due to its quaternary ammonium structure limiting BBB penetration ✓
• D Inhibition of substance P in the enteric nervous system without opioid receptor interaction

Explanation

Methylnaltrexone is a quaternary ammonium derivative of naltrexone; the permanent positive charge prevents it from crossing the blood-brain barrier, so it selectively antagonizes peripheral mu-opioid receptors in the enteric nervous system that mediate slowed GI motility. Central mu receptor-mediated analgesia is preserved because the drug cannot enter the CNS. This is the pharmacological basis of its approved indication for opioid-induced constipation in adults receiving palliative care.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.