Sodium oxybate (gamma-hydroxybutyrate/GHB) is used in narcolepsy with cataplexy. Its mechanism for improving cataplexy and sleep consolidation involves:
- A Selective orexin-2 receptor agonism restoring lost hypocretin signaling
- B Dopamine reuptake inhibition increasing wakefulness drive during the day
- C GABA-B receptor agonism and activation of specific GHB receptors consolidating slow-wave sleep and reducing nocturnal arousals that trigger cataplexy ✓
- D Histamine H1 receptor agonism stabilizing the wake-promoting tuberomammillary nucleus
Correct answer: C. GABA-B receptor agonism and activation of specific GHB receptors consolidating slow-wave sleep and reducing nocturnal arousals that trigger cataplexy
Explanation
GHB acts at both GABA-B receptors (which mediate its sedative/anesthetic effects at high doses) and specific GHB receptors, a subtype of GABA-B family. At therapeutic doses in narcolepsy, it consolidates nocturnal sleep architecture, particularly increasing slow-wave (stage 3) sleep depth. This reduces the excessive fragmented sleep that leads to daytime sleepiness, and also reduces the abnormal intrusions of REM-sleep features (atonia) into wakefulness that manifest as cataplexy, sleep paralysis, and hypnagogic hallucinations.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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