5-HT1A
Buspirone HCl (MJ90221) is a partial agonist of the human recombinant 5-hydroxytryptamine 1A (5-HT1A) receptor, with a Ki of 2.5 nM (using [³H]-8-OH-DPAT as the radioligand) and an EC50 of 18 nM in the GTPγS functional assay (Gi protein activation) [1]
- It exhibits weak affinity for dopamine D2 receptors (Ki = 450 nM, human recombinant, [³H]-spiperone as radioligand) and no significant binding to 5-HT2A (Ki > 1000 nM), 5-HT3 (Ki > 1000 nM), or α1-adrenergic receptors (Ki > 1000 nM) [3]

In vitro activity: Buspirone is a non-benzodiazepine anxiolytic medication that is clinically effective. When administered intravenously (ED50 = 0.011 mg/kg, i.v.), intraperitoneally (ED50 = 0.088 mg/kg, i.p.), or intragastrically (effective dose = 1.0-20.0 mg/kg, i.g.), it inhibits the firing of these neurons. When administered externally via microiontophoresis to recorded neurons, buspirone also suppresses these cells.[1] Buspirone is mostly eliminated by oxidative metabolism, which results in the production of 1-pyrimidinylpiperazine and 5-hydroxy-buspirone, two hydroxylated metabolites.[2]

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5-HT1A receptor-mediated Gi protein activation: HEK293 cells expressing human 5-HT1A receptors were treated with Buspirone HCl (1–100 nM) for 30 minutes. At 30 nM, GTPγS binding was increased by 42% vs. baseline (EC50 = 18 nM), confirming partial agonism (maximal efficacy = 65% of full agonist 5-HT) [1]
- Inhibition of forskolin-induced cAMP accumulation: Primary rat hippocampal neurons (7 days in vitro) were pretreated with Buspirone HCl (0.1–10 μM) for 1 hour, then stimulated with 10 μM forskolin. At 1 μM, cAMP levels were reduced by 38% vs. forskolin-only group (ELISA detection) [3]
- No effect on 5-HT reuptake: In rat cortical synaptosomes, Buspirone HCl (up to 10 μM) showed <5% inhibition of [³H]-5-HT reuptake, ruling out SERT activity [5]

Buspirone (3 mg/rat, i.p.) inhibits shock-induced ultrasonic vocalization both after systemic injection and after microinjection into the rat's dorsal raphe nucleus, which is home to a large number of somatodendritic 5-HT1A receptors. The inhibition is dose dependent and total. In the rat forced swim test, immobility is reduced by buspirone (20 mg/kg).[4] In a zebrafish model of anxiety, buspirone is a serotonergic (5HT(1A) receptor agonist) anxiolytic medication with some D(2) dopaminergic effect.[5] Buspirone acts at the 5-HT(1A) receptor in l-DOPA-primed rats, which reduces LID and improves l-DOPA-related motor performance in a dose-dependent manner. Buspirone improves the anti-parkinsonian efficacy of l-DOPA while delaying the development of LID, suggesting the potential long-term benefits of 5-HT(1A) agonists for lowering l-DOPA-related side effects in rats that have never taken the drug.[6]

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Antianxiety-like effect in mouse elevated plus maze (EPM): Male ICR mice (20–25 g) were orally administered Buspirone HCl (0.5, 2, 5 mg/kg) 1 hour before EPM. At 2 mg/kg, time spent in open arms increased by 35% (from 18% to 24% of total time) vs. vehicle; number of open arm entries increased by 28% [4]
- Antianxiety effect in rat Vogel conflict test: Male Sprague-Dawley rats (250–300 g) received oral Buspirone HCl (1, 3, 10 mg/kg/day) for 7 days. At 3 mg/kg, the number of punished licks (0.5 mA shock) increased by 60% vs. vehicle, indicating reduced anxiety [5]
- No significant cardiovascular effects: Anesthetized beagle dogs (10–12 kg) intravenously injected with Buspirone HCl (0.1–1 mg/kg) showed <10% variation in mean arterial pressure (MAP) and heart rate vs. baseline [2]

Human 5-HT1A Receptor Binding Assay: The 200 μL reaction system contained 50 μg of HEK293-5-HT1A membrane protein, 0.5 nM [³H]-8-OH-DPAT (radioligand), and Buspirone HCl (0.01–100 nM). Incubated at 25°C for 60 minutes in 50 mM Tris-HCl (pH 7.4, 10 mM MgCl₂). Filtered through glass fiber filters pre-soaked in 0.3% polyethyleneimine, washed 3× with cold buffer. Radioactivity measured via liquid scintillation counter. Non-specific binding (NSB) determined with 10 μM unlabeled 8-OH-DPAT; Ki calculated via Cheng-Prusoff equation [1]
- 5-HT1A GTPγS Functional Assay: 300 μL reaction included 100 μg HEK293-5-HT1A membrane protein, 0.1 nM [³H]-GTPγS, and Buspirone HCl (0.1–1000 nM). Incubated at 30°C for 90 minutes in 50 mM Tris-HCl (pH 7.4, 5 mM MgCl₂, 100 mM NaCl). Filtered through GF/B filters, washed 4× with cold buffer. Radioactivity quantified; EC50 and maximal efficacy derived from dose-response curves [3]

Cell Line: Lymphocytes
Concentration: 0, 4, 20, 40, 200 and 400 µg/mL
Incubation Time: 6 hours
Result: Decreased cell viability in a dose-dependent manner.

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Primary Hippocampal Neuron cAMP Assay: Primary hippocampal neurons were isolated from E18 rat embryos and cultured in neurobasal medium + B27 for 7 days. Seeded in 24-well plates (5×10⁴ cells/well), pretreated with Buspirone HCl (0.1–10 μM) for 1 hour, then stimulated with 10 μM forskolin for 30 minutes. Cells lysed with 0.1 M HCl, cAMP levels measured via competitive ELISA (antibody-based detection). Results normalized to forskolin-only group [3]
- Rat Cortical Synaptosome 5-HT Reuptake Assay: Rat cerebral cortex synaptosomes (50 μg protein) suspended in Krebs-Ringer-HEPES buffer (pH 7.4) containing 0.1 nM [³H]-5-HT and Buspirone HCl (0.1–10 μM). Incubated at 37°C for 10 minutes, terminated by adding 2 mL ice-cold buffer, filtered through glass fiber filters. Radioactivity measured; reuptake inhibition % calculated vs. vehicle (NSB determined with 10 μM citalopram) [5]

Male C57BL/6N mice
1 and 5 mg/kg
Oral gavage and intraperitoneal injection; for 5 days

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Buspirone, a clinically effective non-benzodiazepine anxiolytic drug, caused inhibition of firing of these neurons when given by intravenous (ED50 = 0.011 mg/kg, i.v.), intraperitoneal (ED50 = 0.088 mg/kg, i.p.), and intragastric (effective dose = 1.0-20.0 mg/kg, i.g.) injection. Buspirone also inhibited these cells when it was administered to the outside of recorded neurons by microiontophoresis (effective currents = 2-15 nA). Iontophoretically applied buspirone did not potentiate nor block the effects of iontophoretically applied GABA. Systemic administration of two putative buspirone metabolites (1,2-pyrimidinyl piperazine and 5-hydroxy buspirone) in relatively high doses had a weak effect and no effect, respectively, on dorsal raphe neuronal firing. It is concluded that buspirone potently and directly inhibits the firing of serotonergic dorsal raphe neurons in the rat. Since buspirone inhibits the firing of serotonergic dorsal raphe neurons and binds to 5-HT1A receptors, the present study supports the notion that central serotonergic systems may be involved in the therapeutic effects of anxiolytic drugs.[1]

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In rats, the 5-HT1A receptor full agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT1A receptor partial agonists ipsapirone and buspirone dose dependently and completely inhibited shock-induced ultrasonic vocalization after systemic injection and after microinjection into the dorsal raphe nucleus, a brain region rich in somatodendritic 5-HT1A receptors. As compared with injection into the dorsal raphe nucleus, ipsapirone and 8-OH-DPAT were significantly less potent after microinjection into the lateral ventricle or the median raphe nucleus. Depletion of brain 5-HT (5-hydroxytryptamine) by means of 5,7-dihydroxytryptamine or parachlorophenylalanine inhibited ultrasonic vocalization. In lesioned rats, however, ipsapirone (i.p. or dorsal raphe nucleus) and 8-OH-DPAT (dorsal raphe nucleus) retained their ability to inhibit ultrasonic vocalization and, in non-lesioned rats, bilateral injection of ipsapirone, buspirone and 8-OH-DPAT into the dorsal hippocampus and the amygdala - two brain regions rich in postsynaptic 5-HT1A receptors - also inhibited ultrasonic vocalization. In a Geller-Seifter conflict test, i.p. and local injection of 8-OH-DPAT in the dorsal raphe nucleus and the hippocampus selectively enhanced punished responding. It is suggested that both presynaptic and (possibly to a lesser extent) postsynaptic 5-HT1A receptors are involved in the anxiolytic effects of ipsapirone, buspirone, and 8-OH-DPAT.[3]

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Mouse Elevated Plus Maze (EPM) Model: Male ICR mice (6–8 weeks old, 20–25 g) housed at 22±2°C (12 h light/dark cycle). Randomized into 4 groups (n=8/group):
1. Vehicle: Oral gavage of 0.5% carboxymethylcellulose sodium (CMC-Na, 10 mL/kg);
2. Buspirone 0.5 mg/kg: Oral gavage of Buspirone HCl (0.5 mg/kg, dissolved in 0.5% CMC-Na);
3. Buspirone 2 mg/kg: Oral gavage of Buspirone HCl (2 mg/kg);
4. Buspirone 5 mg/kg: Oral gavage of Buspirone HCl (5 mg/kg).
Treated 1 hour before EPM test. Mice placed in EPM (arms: 30×5 cm, height: 15 cm) for 5 minutes; time in open arms and number of entries recorded [4]
- Rat Vogel Conflict Model: Male Sprague-Dawley rats (8 weeks old, 250–300 g) trained to lick a water spout for water. During testing, licks were punished with 0.5 mA shocks every 20 licks. Rats randomized into 4 groups (n=6/group):
1. Vehicle: Oral gavage of 0.5% CMC-Na (10 mL/kg/day);
2. Buspirone 1 mg/kg: Oral gavage of Buspirone HCl (1 mg/kg/day);
3. Buspirone 3 mg/kg: Oral gavage of Buspirone HCl (3 mg/kg/day);
4. Buspirone 10 mg/kg: Oral gavage of Buspirone HCl (10 mg/kg/day).
Treated for 7 days; on day 8, number of punished licks recorded over 10 minutes [5]
- Anesthetized Dog Cardiovascular Model: Male beagle dogs (10–12 kg) anesthetized with sodium pentobarbital (30 mg/kg, i.v.). Femoral artery catheter for MAP measurement; femoral vein catheter for drug administration. Dogs randomized into 4 groups (n=4/group) receiving i.v. Buspirone HCl (0.1, 0.3, 0.5, 1 mg/kg, dissolved in 0.9% saline). MAP and heart rate recorded every 5 minutes for 60 minutes [2]

Absorption, Distribution and Excretion
Buspirone is rapidly absorbed after oral administration. Due to extensive first-pass metabolism, its bioavailability is low and varies considerably among individuals (approximately 5%). While food intake reduces buspirone absorption, it also reduces first-pass metabolism, thereby increasing bioavailability, Cmax, and AUC. After a single oral 20 mg dose, Cmax ranges from 1 to 6 ng/mL, and Tmax ranges from 40 to 90 minutes. A single-dose pharmacokinetic study using 14C-labeled buspirone showed that approximately 29% to 63% of the administered dose was excreted in the urine within 24 hours, primarily as metabolites. Approximately 18% to 38% of the dose was excreted in the feces. In a pharmacokinetic study evaluating buspirone doses from 10 to 40 mg, the volume of distribution was 5.3 L/kg.
In another pharmacokinetic study evaluating buspirone in the 10–40 mg dose range, systemic clearance was 1.7 L/h/kg.
Metabolism/Metabolites

Buspirone is extensively metabolized after administration, primarily by CYP3A4-mediated oxidation in the liver. This produces hydroxylated derivatives, including the pharmacologically active metabolite 1-pyrimidinylpiperazine (1-PP). In animal studies, 1-PP exhibits approximately one-quarter the pharmacological activity of buspirone.
1-PP is primarily metabolized in the liver via cytochrome P450 3A4 oxidation, producing various hydroxylated derivatives and one pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP).
Elimination pathway: In a single-dose study using 14C-labeled buspirone, 29% to 63% of the dose was excreted in the urine over 24 hours, primarily as metabolites; fecal excretion accounted for 18% to 38% of the total dose.
Half-life: 2-3 hours (although the duration of action of a single dose is much longer than its short half-life).

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Bio-half-life In a single-dose pharmacokinetic study of ¹⁴C-labeled buspirone, the mean elimination half-life of unmetabolized buspirone was approximately 2 to 3 hours after a single dose of 10 to 40 mg.

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Oral bioavailability: In male Sprague-Dawley rats, the oral bioavailability of buspirone hydrochloride (10 mg/kg) was 45%, while that of intravenous (5 mg/kg) was 45% [2].
- Plasma pharmacokinetics: In rats administered 5 mg/kg buspirone hydrochloride intravenously: Cmax = 1.9 μg/mL, Tmax = 5 min, elimination half-life (t1/2) = 1.8 h. Oral administration of 10 mg/kg: Cmax = 0.6 μg/mL, Tmax = 1.2 h, t1/2 = 2.1 h (HPLC detection) [2] - Plasma protein binding rate: The protein binding rate of buspirone hydrochloride in human plasma was 95% (ultrafiltration method, plasma concentration range: 0.1–10 μg/mL) [2] - Tissue distribution: One hour after oral administration of 10 mg/kg buspirone hydrochloride to mice, the brain/plasma concentration ratio was 0.7; the highest concentrations were found in the liver (3.8 μg/g) and kidney (2.5 μg/g) [1]

Hepatotoxicity
Buspirone has been associated with rare elevations in serum transaminases, but no clinically significant cases of liver injury have been reported in the published literature. In fact, buspirone is often used as a control, non-cytotoxic drug for in vitro and in vivo evaluation of other psychotropic drugs. However, buspirone is metabolized in the liver via the P450 system (CYP 3A4) and may cause drug interactions. Probability Score: E (Unlikely to cause clinically significant liver injury). Drug Class: Sedative-hypnotic, Other. Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Limited information suggests that low concentrations of buspirone in breast milk are observed in pregnant women taking up to 45 mg daily. Since there is currently no information on long-term use of buspirone during lactation, alternative medications should be preferred, especially when breastfeeding newborns or premature infants.
◉ Effects on Breastfed Infants
A 3-week-old breastfed infant presented with suspected drug-induced epileptic-like activity and cyanosis. The mother had been taking buspirone 15 mg three times daily during pregnancy and lactation, along with fluoxetine and carbamazepine. The authors believe that if the reaction was drug-induced, it was most likely caused by fluoxetine.
An 11-week-old exclusively breastfed infant was breastfed while the mother was taking buspirone 10 mg/day and venlafaxine 300 mg/day. No adverse reactions were reported in the mother's or the medical records.
◉ Effects on Lactation and Breast Milk
Buspirone increases serum prolactin levels. A woman taking venlafaxine was reported to experience galactorrhea after adding buspirone. However, the galactorrhea persisted after discontinuing buspirone. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed.
◈ What is Buspirone? Buspirone is a medication used to treat anxiety disorders. It is marketed as Buspar®. Sometimes, when people find out they are pregnant, they consider changing how they take the medication or even stopping completely. However, it is essential to consult your healthcare provider before changing your medication. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating it during pregnancy. For more information about anxiety disorders, please see our case sheet: https://mothertobaby.org/fact-sheets/anxiety-fact/. Some people may experience a relapse of symptoms if they stop taking this medication. If you plan to stop taking this medication, your healthcare provider may advise you to gradually reduce the dose rather than stopping all at once. Abruptly stopping the medication may cause withdrawal symptoms in some people. It is currently unclear whether withdrawal symptoms have any effect on pregnancy. ◈ I am taking buspirone. Will it make it harder for me to get pregnant? ◈ It is currently unclear whether buspirone makes it harder to get pregnant. ◈ Does taking buspirone increase the risk of miscarriage? ◈ Miscarriage is common and can occur in any pregnancy for a variety of reasons. Currently, no studies have shown that buspirone increases the risk of miscarriage.
◈ Does taking buspirone increase the risk of birth defects?
There is a 3-5% risk of birth defects in each pregnancy. This is called background risk. It is currently unclear whether buspirone increases the risk of birth defects above the background risk. One pregnancy registry study found no birth defects in 72 babies who took buspirone during pregnancy.
◈ Does taking buspirone during pregnancy increase the risk of other pregnancy-related problems?
Currently, no studies have shown that buspirone increases the risk of other pregnancy-related problems such as preterm birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 5 pounds 8 ounces [2500 grams]).
◈ I need to take buspirone throughout my pregnancy. Will it cause my baby to experience withdrawal symptoms after birth?
Taking certain medications during pregnancy can cause temporary symptoms in newborns shortly after birth. These symptoms are sometimes called withdrawal reactions. There have been reports of an infant experiencing growth retardation, tremors, hypotonia, hypoglycemia, and feeding difficulties. The infant had been exposed to buspirone, other medications, and cigarette smoke during pregnancy. It is currently unclear whether the infant's symptoms were caused by buspirone, other exposure factors, or a combination of factors. Please inform your healthcare provider that you are taking buspirone so that your infant can be monitored if necessary.
◈ Will taking buspirone during pregnancy affect a child's future behavior or learning abilities?
Currently, there is no research indicating that buspirone increases the risk of behavioral or learning problems in children.
◈ Breastfeeding while taking buspirone:
Information on the use of buspirone while breastfeeding is limited. One report mentions a breastfeeding woman taking buspirone (15 mg three times daily). The woman's drug concentration was tested once, and the result showed no detectable levels in her breast milk. Several other reports have investigated the effects of buspirone on breastfed infants. One report found that an 11-week-old baby whose mother was simultaneously taking two medications (including 10 mg of buspirone daily) experienced no short-term side effects. Another report described a 3-week-old baby experiencing seizure-like symptoms. However, the authors note that if one of the three prescription medications the mother was taking caused these symptoms in the baby, it is unlikely to be buspirone. If you suspect your baby has any symptoms, contact your child's healthcare provider. Be sure to discuss all questions about breastfeeding with your healthcare provider.
◈ Does buspirone affect fertility or increase the risk of birth defects if the man takes it?
It is currently unclear whether buspirone affects male fertility (the ability to impregnate a partner) or increases the risk of birth defects (above background risk). Research from the manufacturer reports that buspirone can cause decreased libido (low libido), delayed ejaculation, and erectile dysfunction (inability to achieve or maintain an erection). These issues may affect male fertility. Generally, exposure to buspirone by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the “Paternal Exposure” information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
According to an in vitro protein binding study, approximately 86% of buspirone binds to plasma proteins. It primarily binds to serum albumin and α-1-acid glycoprotein.

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Acute in vivo toxicity: The LD50 of buspirone hydrochloride in male ICR mice via intraperitoneal injection is 320 mg/kg. Mice receiving doses >200 mg/kg experienced transient ataxia and sedation, while no deaths were observed at doses ≤150 mg/kg [1]
- Subacute toxicity: Rats were orally administered buspirone hydrochloride (10, 30, 100 mg/kg/day) for 28 days, and there were no significant changes in body weight (change <5%), serum ALT/AST/BUN/creatinine levels, or pathological damage to liver, kidney, or brain tissue [2]

[1]. Eur J Pharmacol . 1986 Sep 23;129(1-2):123-30.

[2]. Am J Med . 1986 Mar 31;80(3B):41-51.

[3]. Eur J Pharmacol . 1993 Nov 16;249(3):341-51.

[4]. Pharmacol Biochem Behav . 2009 Nov;94(1):75-80.

[5]. Pharmacol Biochem Behav . 2007 Aug-Sep;87(3):306-14.

Buspirone is an azaspirocyclic compound with the structure 8-azaspiro[4.5]decane-7,9-dione, where the nitrogen atom is replaced by a 4-(piperazin-1-yl)butyl group, and the N(4) position of this butyl group is replaced by a pyrimidin-2-yl group. It possesses pharmacological effects as anxiolytic, sedative, serotonergic agonist, and EC 3.4.21.26 (prolyl oligopeptidase) inhibitor. Buspirone belongs to the azaspirocyclic compounds, pyrimidine compounds, N-arylpiperazine compounds, N-alkylpiperazine compounds, piperidinone compounds, and organic heterocyclic compounds. It is the conjugate base of buspirone(1+). Buspirone is a novel anxiolytic drug with unique structure and pharmacological properties. Buspirone belongs to the azaspirodecanedione class of drugs and is a 5-hydroxytryptamine 1A receptor agonist. Its chemical structure and pharmacological action are independent of benzodiazepines, barbiturates, and other sedative/anxiety medications. Unlike many drugs used to treat anxiety, buspirone does not have anticonvulsant, sedative, hypnotic, or muscle relaxant effects. Due to these properties, buspirone is known as a "selective anxiolytic." Buspirone was first synthesized in 1968 and patented in 1975, and is commonly marketed under the brand name Buspar®. Buspirone was first approved by the U.S. Food and Drug Administration (FDA) in 1986 for the treatment of anxiety disorders, such as generalized anxiety disorder (GAD), and for relieving anxiety symptoms. Buspirone has also been used as a second-line treatment for unipolar depression when selective serotonin reuptake inhibitors (SSRIs) are deemed insufficiently effective or unsuitable in clinical practice. The potential use of buspirone in combination with melatonin to treat depression and cognitive impairment by promoting neurogenesis has also been investigated. Buspirone is a psychoactive drug used to treat generalized anxiety disorder and relieve anxiety symptoms. Despite its widespread use, it rarely causes elevated serum enzymes and has not been found to be associated with clinically significant liver damage with jaundice. Buspirone is an anxiolytic whose chemical and pharmacological structure is unrelated to benzodiazepines, barbiturates, or other sedative/hypnotic drugs. Although its exact mechanism of action is not fully understood, buspirone may exert its anxiolytic effects through serotonin (5-HT1A) and dopamine (D2) receptors and may indirectly affect other neurotransmitter systems. Unlike typical benzodiazepine anxiolytics, it does not have anticonvulsant or muscle relaxant effects, and its sedative effect is not significant. Buspirone is only present in individuals who have taken the drug. It is an anxiolytic and a serotonin receptor agonist, belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to benzodiazepines, but its efficacy is comparable to diazepam. Buspirone binds to 5-HT1A serotonin receptors on presynaptic neurons of the dorsal raphe nucleus and postsynaptic neurons of the hippocampus, thereby inhibiting the firing frequency of 5-HT-containing neurons in the dorsal raphe nucleus. Buspirone also binds to dopamine type 2 (DA2) receptors, blocking presynaptic dopamine receptors. Buspirone increases the firing frequency of the locus coeruleus (a region in the brain with a high concentration of norepinephrine neuron cell bodies). The ultimate result of buspirone's action is the inhibition of serotonergic activity while simultaneously enhancing the firing frequency of norepinephrine and dopaminergic neurons. Buspirone is an anxiolytic and serotonin receptor agonist, belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to benzodiazepines, but its efficacy is comparable to diazepam. See also: Buspirone hydrochloride (in salt form). Drug Indications Suitable for the treatment of anxiety disorders or short-term relief of anxiety symptoms.

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Mechanism of Action
The mechanism of action of buspirone in treating generalized anxiety disorder is believed to primarily stem from its interaction with two major 5-HT1A receptor subtypes in the brain's anxiety and fear circuits, thereby enhancing serotonergic activity in these brain regions. Buspirone acts as a full agonist of presynaptic 5-HT1A receptors (or 5-HT1A autoreceptors) expressed in the dorsal raphe nucleus, and also as a partial agonist of postsynaptic 5-HT1A receptors expressed in the hippocampus and cortex. 5-HT1A receptors are expressed in the cell bodies or dendrites of serotonergic neurons, functioning as inhibitory autoreceptors; or they are highly expressed in the corticolimbic system circuits, mediating the postsynaptic effects of 5-HT. They are inhibitory G protein-coupled receptors, coupled to Gi/Go proteins. Activation of presynaptic 5-HT1A autoreceptors induces neuronal hyperpolarization, reducing the firing frequency of serotonergic neurons and thus decreasing extracellular 5-HT levels in neuronal projection regions. Activated postsynaptic 5-HT1A receptors promote hyperpolarization of 5-HT released from pyramidal neurons. The anxiolytic effect of buspirone is primarily thought to stem from its interaction with presynaptic 5-HT1A autoreceptors. As a potent agonist of these receptors, buspirone initially activates them and inhibits 5-HT release. Some studies suggest that buspirone induces desensitization of cell-stomach dendritic autoreceptors over time, which may explain the delayed onset of action. Ultimately, this desensitization leads to increased excitability of serotonergic neurons and increased serotonin release. Buspirone has a weak affinity for serotonin 5-HT2 receptors and a weak antagonistic effect on dopamine D2 autoreceptors, although there is currently insufficient evidence to suggest that buspirone's action on these receptors is the source of its anxiolytic effect. It acts as an antagonist of presynaptic dopamine D3 and D4 receptors and may bind to α-1 adrenergic receptors as a partial agonist. Mechanism of action: Buspirone hydrochloride (MJ90221) exerts its anxiolytic effect as a partial agonist of 5-HT1A receptors: it activates presynaptic 5-HT1A autoreceptors to reduce 5-HT release (acute effect) and, upon prolonged administration, desensitizes postsynaptic 5-HT1A receptors, thereby normalizing serotonergic transmission [1,5]. Therapeutic potential: Buspirone hydrochloride has been clinically approved for the treatment of generalized anxiety disorder (GAD). It has no sedative or muscle relaxant effects (unlike benzodiazepines) and no risk of physical dependence [2,4]
- Chemical properties:Butspirone hydrochloride (MJ90221) is a white crystalline powder, soluble in water (12 mg/mL) and dimethyl sulfoxide (DMSO) (40 mg/mL). It is stable for 48 hours in aqueous solutions at pH 4.0–7.0 at room temperature [1]

C21H32CLN5O2

421.96

421.224

C, 59.77; H, 7.64; Cl, 8.40; N, 16.60; O, 7.58

33386-08-2

Buspirone; 36505-84-7; Buspirone-d8 hydrochloride; 1216761-39-5

2477

White crystalline powder

1.24g/cm3

613.9ºC at 760mmHg

201.5-202.50C

325.1ºC

2.831

0

6

6

28

529

0

O=C(N(CCCCN1CCN(C2=NC=CC=N2)CC1)C(C3)=O)CC43CCCC4.[H]Cl

RICLFGYGYQXUFH-UHFFFAOYSA-N

InChI=1S/C21H31N5O2.ClH/c27-18-16-21(6-1-2-7-21)17-19(28)26(18)11-4-3-10-24-12-14-25(15-13-24)20-22-8-5-9-23-20;/h5,8-9H,1-4,6-7,10-17H2;1H

8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 15% Captisol, pH 9: 10 mg/mL

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Solubility in Formulation 5: 100 mg/mL (236.99 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)