Receptors Affected in Buspirone (Buspar) Overdose
In buspirone overdose, the primary receptors affected are serotonin 5-HT1A receptors (where buspirone acts as a partial agonist) and dopamine D2 receptors (where it acts as an antagonist), with secondary effects on noradrenergic and other neurotransmitter systems. 1, 2
Primary Receptor Targets
Serotonin 5-HT1A Receptors:
- Buspirone has high affinity for serotonin 5-HT1A receptors and functions as a partial agonist at these sites 1, 2
- This is the primary mechanism through which buspirone exerts its pharmacological effects 2, 3
- In overdose, excessive 5-HT1A receptor stimulation can lead to serotonin syndrome-like symptoms, though buspirone has relatively low toxicity 1, 2
Dopamine D2 Receptors:
- Buspirone has moderate affinity for brain D2-dopamine receptors, where it acts as an antagonist at presynaptic inhibitory D2 autoreceptors 1, 2
- This antagonism enhances dopaminergic neuron firing rates 4
- Overdose may amplify dopaminergic effects, contributing to agitation or movement-related symptoms 2, 4
Secondary Receptor and Neurotransmitter Effects
Serotonin 5-HT2 Receptors:
- Buspirone has weak affinity for 5-HT2 receptors 2, 3
- This contributes to its overall serotonergic profile but is not the primary mechanism of action 3
Noradrenergic System:
- At therapeutic doses, buspirone increases noradrenaline levels through central mechanisms 4
- In overdose, this can lead to elevated peripheral noradrenaline concentrations and sympathetic activation 4
- This effect is mediated through sympathetic nerves rather than adrenal glands 4
Other Neurotransmitter Systems:
- Buspirone may have indirect effects on glutamatergic, cholinergic, and other neurotransmitter systems 1, 5
- These effects are mediated through the wide distribution of 5-HT1A receptors on various neuronal types 5
Critical Distinctions from Benzodiazepines
GABA Receptors NOT Affected:
- Buspirone has no significant affinity for benzodiazepine receptors 1, 2
- It does not affect GABA binding in vitro or in vivo 1
- Therefore, flumazenil (a benzodiazepine antagonist) has no role in buspirone overdose management 1
Clinical Manifestations of Receptor Effects in Overdose
Serotonergic Effects:
- Mental status changes (confusion, agitation) from excessive 5-HT1A stimulation 6, 2
- Potential for serotonin syndrome when combined with other serotonergic agents 6
Cardiovascular Effects:
- Increased free serotonin can lead to decreased systolic blood pressure and heart rate through parasympathetic activation 4
- Noradrenergic stimulation may cause elevated blood pressure and tachycardia 4
- These opposing effects create variable cardiovascular presentations in overdose 4
Neurological Effects:
- Dizziness, nervousness, and lightheadedness from combined receptor effects 3
- Minimal sedation compared to benzodiazepines due to lack of GABA effects 1, 3
Key Clinical Pitfall
Do not treat buspirone overdose with flumazenil – buspirone does not bind to benzodiazepine receptors, so benzodiazepine antagonists are ineffective and inappropriate 1, 2. Management should focus on supportive care addressing serotonergic and dopaminergic effects rather than GABA-mediated toxicity.