Buspirone, sold under the brand name Buspar, among others, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field an ...

primarily used to treat

anxiety disorders Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

, particularly

generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functio ...

. Benefits support its short-term use. It is taken by mouth, and it may take up to four weeks to have an effect. Common side effects of buspirone include nausea, headaches, dizziness, and difficulty concentrating. Serious side effects may include

hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include h ...

, and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

. Its use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

appears to be safe but has not been well studied, while use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

has not been well studied. It is a serotonin 5-HT_1A receptor

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

. Buspirone was first made in 1968 and approved for medical use in the United States in 1986. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active c ...

. In 2020, it was the 55th most-commonly prescribed medication in the United States, with more than 12million prescriptions.

Medical uses

Anxiety

Buspirone is used for the short-term and long-term treatment of

anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

s or symptoms of anxiety. It is generally preferred over

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

because it does not activate the receptors that make drugs like

alprazolam Alprazolam, sold under the brand name Xanax, among others, is a fast-acting, potent tranquilizer of medium duration in the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It is most commonly ...

addictive. Buspirone has no immediate anxiolytic effects, and hence has a delayed

onset of action Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration. With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question. Other meth ...

; its full clinical effectiveness may require 2–4 weeks to manifest itself. The drug has been shown to be similarly effective in the treatment of generalized anxiety disorder (GAD) to

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s including

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...

lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, insomnia, trouble sleeping, Psychomotor agitation, severe agitation, active Epileptic seizure, seizures including ...

, and

clorazepate Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiaz ...

. Buspirone is not known to be effective in the treatment of other

s besides GAD, although there is some limited evidence that it may be useful in the treatment of

social phobia Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impaired ability to function in at least some aspects o ...

as an adjunct to

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

s (SSRIs).

Other uses

Sexual dysfunction

There is some evidence that buspirone on its own may be useful in the treatment of hypoactive sexual desire disorder (HSDD) in women.

Miscellaneous

Buspirone is not effective as a treatment for benzodiazepine withdrawal, barbiturate withdrawal, or

alcohol withdrawal Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...

delirium tremens Delirium tremens (DTs) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shiver ...

. SSRI and SNRI antidepressants such as

paroxetine Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...

and

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic di ...

may cause jaw pain/jaw spasm reversible syndrome (although it is not common), and buspirone appears to be successful in treating

bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the gen ...

on SSRI/SNRI-induced jaw clenching.

Contraindications

Buspirone has these contraindications: * Hypersensitivity to buspirone *

Metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidne ...

, as in

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

* Should not be used with

MAO inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

s * Severely compromised

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and/or

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

function

Side effects

Known

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s associated with buspirone include

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

, and

paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

. Buspirone is relatively well tolerated, and is not associated with

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ethe ...

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...

and psychomotor impairment,

muscle relaxation Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...

physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain ...

, or

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

effects. In addition, buspirone does not produce

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and dan ...

and is not a

drug of abuse Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

. Dyskinesia, akathisia, myoclonus, parkinsonism, and dystonia were reported associated with buspirone. It is unclear if there is a risk of

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

or other movement disorders with buspirone.

Overdose

Buspirone appears to be relatively benign in cases of single-drug

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

, although no definitive data on this subject appear to be available. In one

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

, buspirone was administered to healthy male volunteers at a dosage of 375 mg/day, and produced side effects including

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asle ...

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

, and

gastric distress Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a mor ...

. In early clinical trials, buspirone was given at dosages even as high as 2,400 mg/day, with

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...

, and

muscle rigidity Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending ...

observed. Deliberate overdoses with 250 mg and up to 300 mg buspirone have resulted in drowsiness in about 50% of individuals. One death has been reported in a co-ingestion of 450 mg buspirone with

diltiazem Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be ...

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

Interactions

Buspirone has been shown ''in vitro'' to be

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. This finding is consistent with the ''in vivo'' interactions observed between buspirone and these inhibitors or inducers of

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

3A4 (CYP3A4), among others: *

Itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mout ...

: Increased plasma level of buspirone *

Rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used ...

: Decreased plasma levels of buspirone *

Nefazodone Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant which was first marketed by Bristol-Myers Squibb (BMS) in 1994 but has since largely been discontinued. BMS withdrew it fro ...

: Increased plasma levels of buspirone *

Haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

: Increased plasma levels of buspirone *

Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

: Decreased plasma levels of buspirone * Grapefruit: Significantly increases the plasma levels of buspirone. See

grapefruit–drug interactions Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect is most studied with grapefruit and grapefruit juice, but similar effects have been observed with certain other citrus fruits. ...

. *

Fluvoxamine Fluvoxamine, sold under the brand name Luvox and Faverin among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder ...

: Moderately increase plasma levels of buspirone. Elevated blood pressure has been reported when buspirone has been administered to patients taking monoamine oxidase inhibitors (MAOIs).

Pharmacology

Pharmacodynamics

Buspirone acts as an

of the serotonin 5-HT_1A receptor with high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Part ...

. It is a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonist ...

of both

presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

5-HT_1A receptors, which are inhibitory

autoreceptor An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the a ...

s, and

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

5-HT_1A receptors. It is thought that the main effects of buspirone are mediated via its interaction with the presynaptic 5-HT_1A receptor, thus reducing the firing of serotonin-producing neurons. Buspirone also has lower affinities for the serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆, and 5-HT₇ receptors. In addition to binding to serotonin receptors, buspirone is an antagonist of the

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

D₂ receptor with weak affinity. It preferentially blocks inhibitory presynaptic D₂ autoreceptors, and antagonizes postsynaptic D₂ receptors only at higher doses. In accordance, buspirone has been found to increase

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate do ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

in the

nigrostriatal pathway The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain. It is one of th ...

at low doses, whereas at higher doses, postsynaptic D₂ receptors are blocked and

antidopaminergic A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have f ...

effects such as hypoactivity and reduced

stereotypy A stereotypy (, or ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are ...

, though notably not

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscle, muscular rigidity and fixity of human position, posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and ...

, are observed in animals. Buspirone has also been found to bind with much higher affinity to the dopamine D₃ and D₄ receptors, where it is similarly an antagonist. A major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

of buspirone,

1-(2-pyrimidinyl)piperazine 1-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α2-adrenergic receptor (Ki = 7.3–40 nM) and, to a much lesser extent, as a partial agonist of the 5 ...

(1-PP), occurs at higher circulating levels than buspirone itself and is known to act as a potent α₂-adrenergic receptor antagonist. This metabolite may be responsible for the increased

noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and

activity observed with buspirone in animals. In addition, 1-PP may play an important role in the antidepressant effects of buspirone. Buspirone also has very weak and probably clinically unimportant affinity for the α₁-adrenergic receptor. However, buspirone has been reported to have shown "significant and selective intrinsic efficacy" at the α₁-adrenergic receptor expressed in a "tissue- and species-dependent manner". Unlike benzodiazepines, buspirone does not interact with the GABA_A receptor complex.

Pharmacokinetics

Buspirone has a low

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. ...

of 3.9% relative to

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

due to extensive

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...

. The time to peak plasma levels following ingestion is 0.9 to 1.5 hours. It is reported to have an

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of 2.8 hours, although a review of 14 studies found that the mean terminal half-life ranged between 2 and 11 hours, and one study even reported a terminal half-life of 33 hours. Buspirone is

primarily by

, and prominent

drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the dru ...

s with inhibitors and

inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...

s of this

have been observed. Major

s of buspirone include 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-PP. 6-Hydroxybuspirone has been identified as the predominant

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

metabolite of buspirone, with plasma levels that are 40-fold greater than those of buspirone after oral administration of buspirone to humans. The metabolite is a high-affinity partial agonist of the 5-HT_1A receptor (K_i = 25 nM) similarly to buspirone, and has demonstrated occupancy of the 5-HT_1A receptor ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

''. As such, it is likely to play an important role in the therapeutic effects of buspirone. 1-PP has also been found to circulate at higher levels than those of buspirone itself and may similarly play a significant role in the clinical effects of buspirone. Buspirone metabolism

Chemistry

Buspirone is a member of the

azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Medical uses Azapirones have shown be ...

chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classifica ...

, and consists of

azaspirodecanedione Azaspirodecanedione is a chemical compound. It is a component of the chemical structures of several of the azapirones. See also * Azapirone * Azaspirodecane * Glutarimide * Ketone * Spirodecanedione Spirodecanedione is a chemical compound. ...

and

pyrimidinylpiperazine 1-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α2-adrenergic receptor (Ki = 7.3–40 nM) and, to a much lesser extent, as a partial agonist of the 5 ...

components linked together by a

butyl In organic chemistry, butyl is a four-carbon alkyl radical or substituent group with general chemical formula , derived from either of the two isomers (''n''-butane and isobutane) of butane. The isomer ''n''-butane can connect in two ways, giv ...

chain A chain is a wikt:series#Noun, serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression (physics), compression but line (g ...

Analogues

Structural analogue A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...

s of buspirone include other azapirones like

gepirone Gepirone is an antidepressant and anxiolytic drug of the azapirone group that was synthesized by Bristol-Myers Squibb in 1986 and has been under development for the treatment of depression but has yet to be marketed. It has been under develop ...

ipsapirone Ipsapirone is a selective 5-HT1A receptor partial agonist of the piperazine and azapirone chemical classes. It has antidepressant and anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention t ...

perospirone Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania. Medical uses Its primary uses are i ...

, and

tandospirone Tandospirone (brand name Sediel) is an anxiolytic and antidepressant drug used in China and Japan, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones lik ...

. A number of analogues are recorded.

Synthesis

A number of more modern methods of synthesis have also been reported (list not exhaustive): Buspirone-synthesis

Alkylation of 1-(2-pyrimidyl)piperazine

0980-22-7 98 may refer to: * 98 (number) * Windows 98, a Microsoft operating system Years * 98 BC * AD 98 * 1798 * 1898 * 1998 * 2098 In contemporary history, the third millennium of the anno Domini or Common Era in the Gregorian calendar is the c ...

(1) with 3-chloro-1-cyanopropane (4-chlorobutyronitrile) 28-20-6(2) gives 3386-14-0(3). the reduction of the nitrile group is performed either by

catalytic hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic c ...

or with LAH giving 3386-20-8(4). The primary amine is then reacted with 3,3-tetramethyleneglutaric anhydride 662-95-3(5) in order to yield ' (6).

History

Buspirone was first synthesized by a team at

Mead Johnson Mead Johnson & Company, LLC is an American company that is a leading manufacturer of infant formula, both domestically and globally, with its flagship product Enfamil. It operates as an independent subsidiary of Reckitt. The company dates back t ...

in 1968 but was not patented until 1980. It was initially developed as an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range o ...

acting on the D₂ receptor but was found to be ineffective in the treatment of

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

; it was then used as an anxiolytic instead. In 1986,

Bristol-Myers Squibb The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the l ...

gained FDA approval for buspirone in the treatment of GAD. The

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling disclo ...

expired in 2001, and buspirone is now available as a

generic drug A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

Society and culture

Generic names

''Buspirone'' is the , , , and of buspirone, while ''buspirone hydrochloride'' is its , , and .

Brand name

Buspirone was primarily sold under the brand name Buspar. Buspar is currently listed as discontinued by the US Federal Drug Administration. In 2010, in response to a citizen petition, the US FDA determined that Buspar was not withdrawn from sale for reasons of safety or effectiveness.

2019 shortage

Due to interrupted production at a

Mylan Pharmaceuticals Mylan N.V. was a global generic and specialty pharmaceuticals company. In November 2020, Mylan merged with Upjohn, Pfizer's off-patent medicine division, to form Viatris. Previously, the company was domiciled in the Netherlands, with principal ...

plant in

Morgantown, West Virginia Morgantown is a city in and the county seat of Monongalia County, West Virginia, United States, situated along the Monongahela River. The largest city in North-Central West Virginia, Morgantown is best known as the home of West Virginia Universit ...

, the United States experienced a shortage of buspirone in 2019.

Research

Some tentative research supports other uses such as the treatment of depression and behavioral problems following brain damage.

References

External links

* * {{Portal bar , Medicine 5-HT1A agonists Alpha-2 blockers Antidepressants Anxiolytics Azapirones Cyclopentanes D2 antagonists D3 antagonists D4 antagonists Glutarimides Aminopyrimidines Wikipedia medicine articles ready to translate 1968 in science