Sodium oxybate (GHB, gamma-hydroxybutyrate) is approved for cataplexy in narcolepsy. Its mechanism of action relevant to this indication involves:

• A GHB receptor agonism and GABA-B receptor agonism in the hypothalamus and locus coeruleus, consolidating nighttime sleep and thereby reducing daytime cataplexy ✓
• B Selective orexin (hypocretin) receptor-2 agonism, restoring thalamocortical arousal
• C H1 receptor inverse agonism in the posterior hypothalamus, promoting sleep consolidation
• D Serotonin transporter blockade reducing REM intrusions during wakefulness

Explanation

Sodium oxybate (gamma-hydroxybutyrate) acts on both specific GHB receptors (at low concentrations) and GABA-B receptors (at therapeutic concentrations). In narcolepsy, it consolidates slow-wave sleep at night, thereby reducing abnormal REM intrusions during the day (cataplexy, hypnagogic hallucinations, sleep paralysis). The improvement in cataplexy is not immediate (takes weeks) — thought to relate to tonic GABA-B-mediated suppression of amygdalotrigeminal brainstem circuits that trigger cataplexy. Suvorexant/lemborexant are orexin receptor antagonists used for insomnia — not for cataplexy.

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

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Written and medically reviewed by the StethoPrep medical team.