Top Gene Interactions
- Metabolism: Metabolized hepatically, primarily by oxidation by cytochrome P450 3A4 producing several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP) Route of Elimination: In a single-dose study using 14C-labeled buspirone, 29% to 63% of the dose was excreted in the urine within 24 hours, primarily as metabolites; fecal excretion accounted for 18% to 38% of the dose. Half Life: 2-3 hours (although the action of a single dose is much longer than the short halflife indicates).
- Uses/Sources: For the management of anxiety disorders or the short-term relief of the symptoms of anxiety, and also as an augmention of SSRI-treatment against depression.
- Symptoms: Symptoms of overdose include dizziness, drowsiness, nausea or vomiting, severe stomach upset, and unusually small pupils.
- Treatment: General symptomatic and supportive measures should be used along with immediate gastric lavage. Respiration, pulse, and blood pressure should be monitored as in all cases of drug overdosage. No specific antidote is known to buspirone, and dialyzability of buspirone has not been determined. (L1712)
- Route of Exposure: Oral. Rapidly absorbed in man. Bioavailability is low and variable (approximately 5%) due to extensive first pass metabolism.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 136 mg/kg (Oral, rat)
Mechanism of Action
|Target Name||Mechanism of Action||References|
5-hydroxytryptamine receptor 2A
5-hydroxytryptamine receptor 2C
5-hydroxytryptamine receptor 2B
5-hydroxytryptamine receptor 3A
Sigma non-opioid intracellular receptor 1
Solute carrier family 22 member 2
Multidrug and toxin extrusion protein 1
Multidrug and toxin extrusion protein 2
5-hydroxytryptamine receptor 1A
D(2) dopamine receptor
|Buspirone binds to 5-HT type 1A serotonin receptors on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus, thus inhibiting the firing rate of 5-HT-containing neurons in the dorsal raphe. Buspirone also binds at dopamine type 2 (DA2) receptors, blocking presynaptic dopamine receptors. Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. The net result of buspirone actions is that serotonergic activity is suppressed while noradrenergic and dopaminergic cell firing is enhanced.||