From the FDA Drug Label
The mechanism of action of buspirone is unknown. ... 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.
The FDA drug label does not provide information on the effect of Buspar (buspirone) on the 5-HT2 receptor.
From the Research
Buspar (buspirone) has minimal direct activity at 5-HT2 receptors, showing only weak binding affinity and no meaningful agonist or antagonist effects, with its primary action being as a partial agonist at serotonin 5-HT1A receptors. The therapeutic effects of buspirone in anxiety disorders come mainly from its action at 5-HT1A receptors, where it increases serotonergic activity in specific brain regions while also having some dopamine D2 receptor activity 1. This distinguishes it from other anxiolytic medications like some antipsychotics or certain antidepressants that do target 5-HT2 receptors.
Key Points
- Buspirone's action at 5-HT1A receptors is the primary mechanism for its anxiolytic effects
- The medication has weak affinity for 5-HT2 receptors, with no significant agonist or antagonist effects
- Buspirone is typically prescribed at doses starting at 5mg three times daily, gradually increasing to 20-30mg total daily dose divided throughout the day
- Unlike benzodiazepines, buspirone doesn't cause significant sedation, physical dependence, or withdrawal symptoms, making it suitable for longer-term anxiety management
Clinical Considerations
- Patients should be aware that buspirone typically takes 2-4 weeks to reach full therapeutic effect, unlike the immediate relief provided by benzodiazepines
- The use of buspirone with other serotonergic drugs, such as fluoxetine, may increase the risk of serotonin syndrome 2
- Buspirone's effects on serotonergic systems, including presynaptic and postsynaptic receptors, predict both anxiolytic and antidepressant activity 3