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[td]* The page is cleared regularly *[/td] [td]* Feel free to try your editing skills below *[/td]
[td]* Feel free to try your editing skills below *[/td] [td]β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β -->'''Buspirone''' is an anxiolytic medication primarily used for the treatment of [[generalized anxiety disorder]]. Unlike [[benzodiazepine]]s, buspirone does not produce significant sedation, dependence, or withdrawal effects. Its principal mechanism involves partial agonism at postsynaptic [[serotonin]] 5-HTβA receptors and full agonism at presynaptic 5-HTβA autoreceptors, which initially reduces serotonergic neuron firing. Over time, presynaptic autoreceptors desensitize, leading to increased serotonin release and enhanced serotonergic tone, which may contribute to its clinical efficacy. Buspirone also has weak antagonistic effects at [[dopamine]] D2, D3, and D4 receptors, as well as Ξ±β- and Ξ±β-adrenergic receptors.[/td] [td]β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β -->[/td] [td][/td] [td]==Medical uses==[/td] [td]Buspirone is approved for the management of generalized anxiety disorder. It is sometimes used off-label for other anxiety disorders, depression augmentation, and certain behavioral conditions. Buspirone is not effective as a sedative-hypnotic or muscle relaxant and does not have anticonvulsant properties.[/td] [td][/td] [td]==Pharmacology==[/td] [td][/td] [td]===Pharmacodynamics===[/td] [td]Buspirone acts primarily on the serotonin 5-HTβA receptor. It is a '''full agonist''' at presynaptic 5-HTβA autoreceptors in the dorsal raphe, initially reducing serotonergic neuron firing, and a '''partial agonist''' at postsynaptic 5-HTβA receptors in forebrain regions. Over weeks of treatment, presynaptic autoreceptors desensitize, allowing serotonin neuron firing to increase and enhancing serotonin release, contributing to its anxiolytic effects.<ref name="Smith1986">Smith LM, Peroutka SJ. Differential effects of 5-HTβAβselective compounds on [Β³H]8-OH-DPAT binding and 5-HT behavioral syndrome in rat. ''Eur J Pharmacol.'' 1986;128(1-2):73β80. doi:10.1016/0014-2999(86)90292-9.</ref><ref name="Savitz2009">Savitz J, Lucki I, Drevets WC. 5-HTβA receptor function in major depressive disorder. ''Prog Neurobiol.'' 2009;88(1):17β31. doi:10.1016/j.pneurobio.2009.01.007.</ref><ref name="VanderMaelen1986">VanderMaelen CP, Aghajanian GK. Electrophysiological and pharmacological characterization of 5-HTβA autoreceptors in dorsal raphe. ''Neuropharmacology.'' 1986;25(8):857β862. doi:10.1016/0028-3908(86)90163-0.</ref><ref name="Haleem2019">Haleem DJ. Targeting 5-HTβA receptors for treating chronic pain and depression. ''CNS Neurosci Ther.'' 2019;25(10):1105β1114. doi:10.1111/cns.13223.</ref><ref name="Valdizan2010">ValdizΓ‘n EM, Castro E, Pazos A. Agonist-dependent desensitization of 5-HTβA autoreceptors: implications for antidepressant action. ''Int J Neuropsychopharmacol.'' 2010;13(6):813β828. doi:10.1017/S1461145709990603.</ref>[/td] [td][/td] [td]Buspirone also has lower affinity for other serotonin receptors, including 5-HTβA, 5-HTβB, 5-HTβC, 5-HTβ, and 5-HTβ, where it acts primarily as an antagonist.<ref>Sato et al., 2010</ref> It has weak antagonistic effects at dopamine D2, D3, and D4 receptors, preferentially blocking presynaptic D2 autoreceptors at low doses and postsynaptic D2 receptors at higher doses.<ref>PMID 22608068</ref>[/td] [td][/td] [td]A major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP), circulates at higher levels than buspirone itself and acts as a potent Ξ±β-adrenergic receptor antagonist, which may contribute to enhanced noradrenergic and dopaminergic activity. Buspirone has very weak affinity for Ξ±β-adrenergic receptors and does not interact with the GABA_A receptor complex, unlike benzodiazepines.<ref>PMID 1681447</ref><ref>PMID 1796057</ref>[/td] [td][/td] [td]===Pharmacokinetics===[/td] [td]Buspirone is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 60β90 minutes. It undergoes extensive first-pass metabolism, resulting in low oral bioavailability (~5β10%). The drug is primarily metabolized by the liver enzyme CYP3A4 to several metabolites, including 1-PP. Buspirone has an elimination half-life of approximately 2β3 hours, though the effects of its active metabolite may prolong its pharmacodynamic action. It is excreted mainly in urine as metabolites.[/td] [td][/td] [td]==Side effects==[/td] [td]Common side effects include dizziness, headache, nausea, and nervousness. Unlike benzodiazepines, buspirone does not cause sedation, cognitive impairment, or significant risk of dependence. Rarely, it may cause gastrointestinal upset, akathisia, or mild hypotension.[/td] [td][/td] [td]==Interactions==[/td] [td]Buspirone is metabolized by CYP3A4 and may interact with inhibitors (e.g., ketoconazole, erythromycin) or inducers (e.g., rifampin, carbamazepine), which can increase or decrease plasma levels. Concomitant use with MAO inhibitors or other serotonergic drugs may increase the risk of serotonin syndrome.[/td] [td][/td] [td]==Chemistry==[/td] [td]Buspirone belongs to the azapirone class of compounds. It is structurally unrelated to benzodiazepines, barbiturates, or other major anxiolytics. Its chemical name is 8-[4-(4-pyrimidinyl)-1-piperazinyl]-8-azaspiro[4.5]decane-7,9-dione.[/td] [td][/td] [td]==History==[/td] [td]Buspirone was first synthesized in the 1960s and introduced clinically in the 1980s as a non-sedating anxiolytic alternative to benzodiazepines. It has been primarily used for generalized anxiety disorder.[/td] [td][/td] [td]==Society and culture==[/td] [td]Buspirone is available under various brand names worldwide. It is commonly prescribed as an oral tablet and is included on the WHO Model List of Essential Medicines. It is considered low-risk in terms of abuse and dependence.[/td] [td][/td] [td]==References==[/td] [td]<references />[/td]
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[td]* The page is cleared regularly *[/td]Revision as of 23:30, 2 September 2025
[/td][td]* The page is cleared regularly *[/td] [td]* Feel free to try your editing skills below *[/td]
[td]* Feel free to try your editing skills below *[/td] [td]β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β -->'''Buspirone''' is an anxiolytic medication primarily used for the treatment of [[generalized anxiety disorder]]. Unlike [[benzodiazepine]]s, buspirone does not produce significant sedation, dependence, or withdrawal effects. Its principal mechanism involves partial agonism at postsynaptic [[serotonin]] 5-HTβA receptors and full agonism at presynaptic 5-HTβA autoreceptors, which initially reduces serotonergic neuron firing. Over time, presynaptic autoreceptors desensitize, leading to increased serotonin release and enhanced serotonergic tone, which may contribute to its clinical efficacy. Buspirone also has weak antagonistic effects at [[dopamine]] D2, D3, and D4 receptors, as well as Ξ±β- and Ξ±β-adrenergic receptors.[/td] [td]β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β β -->[/td] [td][/td] [td]==Medical uses==[/td] [td]Buspirone is approved for the management of generalized anxiety disorder. It is sometimes used off-label for other anxiety disorders, depression augmentation, and certain behavioral conditions. Buspirone is not effective as a sedative-hypnotic or muscle relaxant and does not have anticonvulsant properties.[/td] [td][/td] [td]==Pharmacology==[/td] [td][/td] [td]===Pharmacodynamics===[/td] [td]Buspirone acts primarily on the serotonin 5-HTβA receptor. It is a '''full agonist''' at presynaptic 5-HTβA autoreceptors in the dorsal raphe, initially reducing serotonergic neuron firing, and a '''partial agonist''' at postsynaptic 5-HTβA receptors in forebrain regions. Over weeks of treatment, presynaptic autoreceptors desensitize, allowing serotonin neuron firing to increase and enhancing serotonin release, contributing to its anxiolytic effects.<ref name="Smith1986">Smith LM, Peroutka SJ. Differential effects of 5-HTβAβselective compounds on [Β³H]8-OH-DPAT binding and 5-HT behavioral syndrome in rat. ''Eur J Pharmacol.'' 1986;128(1-2):73β80. doi:10.1016/0014-2999(86)90292-9.</ref><ref name="Savitz2009">Savitz J, Lucki I, Drevets WC. 5-HTβA receptor function in major depressive disorder. ''Prog Neurobiol.'' 2009;88(1):17β31. doi:10.1016/j.pneurobio.2009.01.007.</ref><ref name="VanderMaelen1986">VanderMaelen CP, Aghajanian GK. Electrophysiological and pharmacological characterization of 5-HTβA autoreceptors in dorsal raphe. ''Neuropharmacology.'' 1986;25(8):857β862. doi:10.1016/0028-3908(86)90163-0.</ref><ref name="Haleem2019">Haleem DJ. Targeting 5-HTβA receptors for treating chronic pain and depression. ''CNS Neurosci Ther.'' 2019;25(10):1105β1114. doi:10.1111/cns.13223.</ref><ref name="Valdizan2010">ValdizΓ‘n EM, Castro E, Pazos A. Agonist-dependent desensitization of 5-HTβA autoreceptors: implications for antidepressant action. ''Int J Neuropsychopharmacol.'' 2010;13(6):813β828. doi:10.1017/S1461145709990603.</ref>[/td] [td][/td] [td]Buspirone also has lower affinity for other serotonin receptors, including 5-HTβA, 5-HTβB, 5-HTβC, 5-HTβ, and 5-HTβ, where it acts primarily as an antagonist.<ref>Sato et al., 2010</ref> It has weak antagonistic effects at dopamine D2, D3, and D4 receptors, preferentially blocking presynaptic D2 autoreceptors at low doses and postsynaptic D2 receptors at higher doses.<ref>PMID 22608068</ref>[/td] [td][/td] [td]A major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP), circulates at higher levels than buspirone itself and acts as a potent Ξ±β-adrenergic receptor antagonist, which may contribute to enhanced noradrenergic and dopaminergic activity. Buspirone has very weak affinity for Ξ±β-adrenergic receptors and does not interact with the GABA_A receptor complex, unlike benzodiazepines.<ref>PMID 1681447</ref><ref>PMID 1796057</ref>[/td] [td][/td] [td]===Pharmacokinetics===[/td] [td]Buspirone is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 60β90 minutes. It undergoes extensive first-pass metabolism, resulting in low oral bioavailability (~5β10%). The drug is primarily metabolized by the liver enzyme CYP3A4 to several metabolites, including 1-PP. Buspirone has an elimination half-life of approximately 2β3 hours, though the effects of its active metabolite may prolong its pharmacodynamic action. It is excreted mainly in urine as metabolites.[/td] [td][/td] [td]==Side effects==[/td] [td]Common side effects include dizziness, headache, nausea, and nervousness. Unlike benzodiazepines, buspirone does not cause sedation, cognitive impairment, or significant risk of dependence. Rarely, it may cause gastrointestinal upset, akathisia, or mild hypotension.[/td] [td][/td] [td]==Interactions==[/td] [td]Buspirone is metabolized by CYP3A4 and may interact with inhibitors (e.g., ketoconazole, erythromycin) or inducers (e.g., rifampin, carbamazepine), which can increase or decrease plasma levels. Concomitant use with MAO inhibitors or other serotonergic drugs may increase the risk of serotonin syndrome.[/td] [td][/td] [td]==Chemistry==[/td] [td]Buspirone belongs to the azapirone class of compounds. It is structurally unrelated to benzodiazepines, barbiturates, or other major anxiolytics. Its chemical name is 8-[4-(4-pyrimidinyl)-1-piperazinyl]-8-azaspiro[4.5]decane-7,9-dione.[/td] [td][/td] [td]==History==[/td] [td]Buspirone was first synthesized in the 1960s and introduced clinically in the 1980s as a non-sedating anxiolytic alternative to benzodiazepines. It has been primarily used for generalized anxiety disorder.[/td] [td][/td] [td]==Society and culture==[/td] [td]Buspirone is available under various brand names worldwide. It is commonly prescribed as an oral tablet and is included on the WHO Model List of Essential Medicines. It is considered low-risk in terms of abuse and dependence.[/td] [td][/td] [td]==References==[/td] [td]<references />[/td]
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