From the Guidelines
Buspirone works primarily by acting as a partial agonist at serotonin 5-HT1A receptors in the brain, which explains its anxiolytic effects without sedative properties or addiction potential. The mechanism of action of buspirone involves binding to presynaptic 5-HT1A autoreceptors, initially decreasing serotonin release, but with continued use, these autoreceptors become desensitized, ultimately increasing serotonergic neurotransmission 1. Buspirone also binds to postsynaptic 5-HT1A receptors, modulating serotonin activity in brain regions associated with anxiety. Additionally, buspirone has moderate affinity for dopamine D2 receptors, which may contribute to its anxiolytic effects.
The unique mechanism of buspirone explains why it typically requires 2-4 weeks of regular use before therapeutic effects are noticed, unlike the immediate relief provided by benzodiazepines. The medication is typically dosed at 15-30 mg daily, divided into 2-3 doses, with a maximum recommended dose of 60 mg per day, although some studies suggest an initial dosage of 5 mg twice daily, with a maximum of 20 mg three times daily 1. Patients should be aware that buspirone must be taken consistently to maintain its therapeutic effect and is not effective for as-needed anxiety relief.
Some key points to consider when prescribing buspirone include:
- Its use is recommended for patients with mild to moderate agitation
- It may take 2 to 4 weeks to become effective
- It is not effective for as-needed anxiety relief
- It should be taken consistently to maintain its therapeutic effect
- The maximum recommended dose is 60 mg per day, although some studies suggest a lower maximum dose.
Overall, buspirone is a useful medication for the treatment of anxiety, with a unique mechanism of action that distinguishes it from benzodiazepines and other anxiolytic medications.
From the FDA Drug Label
The mechanism of action of buspirone is unknown. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. In vitro preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT1A) receptors Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo when tested in preclinical models. Buspirone has moderate affinity for brain D2-dopamine receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems
The mechanism of action of buspirone is unknown. However, it is known that buspirone:
- Has a high affinity for serotonin (5-HT1A) receptors
- Has no significant affinity for benzodiazepine receptors
- Does not affect GABA binding
- Has moderate affinity for brain D2-dopamine receptors
- May have indirect effects on other neurotransmitter systems 2
From the Research
Mechanism of Action
The mechanism of action for Buspirone is complex and not entirely clear, but it is thought to be mediated mainly through its action as a partial agonist for the serotonin 5-HT(1A) receptors 3, 4, 5, 6.
- Buspirone has a low affinity and acts as an antagonist for the dopamine D(2) autoreceptors 3, 4.
- It also has some evidence of a weak affinity to 5-HT(2) receptors 3, 4.
- The action of buspirone at the 5-HT1A serotonin receptor is supported by studies focused on receptor binding, anatomical localization, biochemistry, neurophysiology, and animal behavior 5.
- Buspirone does not act on the GABA receptor, which is the primary target for benzodiazepines 5, 6.
- Its anxiolytic activity is thought to be due to its ability to attenuate central 5-hydroxytryptamine neurotransmission, specifically by acting as an agonist at presynaptic 5-HT1A receptors, particularly in the raphe nuclei 6.
Comparison to Other Anxiolytics
Buspirone's mechanism of action differs from that of benzodiazepines, which act on the GABA receptor 5, 7, 6.
- Unlike benzodiazepines, buspirone lacks hypnotic, anticonvulsant, and muscle relaxant properties, and has been termed 'anxioselective' 7.
- Buspirone's efficacy is comparable to that of benzodiazepines in the treatment of generalized anxiety disorders, but it has a lower incidence of sedation and other side effects 4, 7.