Buspirone is an anxiolytic with no abuse potential, unlike benzodiazepines. Its mechanism of action is:
- A Partial agonist at 5-HT1A autoreceptors (in raphe nuclei) and postsynaptic 5-HT1A receptors, with mild D2 receptor partial agonism ✓
- B Positive allosteric modulation of GABA-A receptor chloride ionophore
- C Selective norepinephrine reuptake inhibition via NET blockade
- D Antagonist at GABA-B receptors in the locus coeruleus
Explanation
Buspirone is a partial agonist at 5-HT1A receptors. At presynaptic 5-HT1A autoreceptors on serotonergic raphe neurons, it acts as an agonist, reducing serotonin firing rate. At postsynaptic cortical and limbic 5-HT1A receptors, partial agonism attenuates anxiety-related serotonergic signalling. Additionally, buspirone has weak D2 partial agonism (relevant to its inability to treat acute panic attacks). Because it has no GABA-A interaction, buspirone lacks the abuse potential, sedation, tolerance, and physical dependence of benzodiazepines, but requires 2–4 weeks for onset — making it unsuitable for acute anxiety but appropriate for GAD.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.