Regarding benzodiazepine pharmacology, which of the following best explains why zolpidem has fewer anxiolytic and muscle-relaxant effects compared with diazepam despite acting at the same receptor complex?
- A Zolpidem is a partial agonist at GABA-A receptors, producing submaximal chloride conductance
- B Zolpidem selectively binds GABA-A receptors containing the alpha-1 subunit, which mediate sedation but not anxiolysis or muscle relaxation ✓
- C Zolpidem has a longer half-life than diazepam, leading to receptor downregulation over time
- D Zolpidem acts only at peripheral benzodiazepine receptors (TSPO) in peripheral tissue
Correct answer: B. Zolpidem selectively binds GABA-A receptors containing the alpha-1 subunit, which mediate sedation but not anxiolysis or muscle relaxation
Explanation
GABA-A receptors with the alpha-1 subunit mediate sedation and amnesia, while alpha-2 and alpha-3 subunits mediate anxiolysis, muscle relaxation, and anticonvulsant effects. Zolpidem (a non-benzodiazepine Z-drug) selectively binds alpha-1-containing receptors (BZ1 type), accounting for its predominantly hypnotic profile with relatively less anxiolysis or muscle relaxation. Diazepam is non-selective across alpha subunits, producing the full benzodiazepine pharmacological spectrum.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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