Buspirone
Buspirone is an anxiolytic

Anxiolytic

An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

 psychoactive drug

Psychoactive drug

A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...

 of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder (GAD)

Bristol-Myers Squibb

Bristol-Myers Squibb

Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...

 (BMS) gained FDA approval

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 of buspirone in 1986 for treatment of GAD. The patent on Buspar by Bristol-Myers Squibb expired in 2001, and buspirone is available as a generic

Generic drug

A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...

.

Medical uses

• Generalized anxiety disorder (GAD) of very mild to moderate intensity, without any panic attack
  Panic attack
  Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...
  
  s (it is not generally considered to be effective, nor does it have regulatory approval for other types of anxiety disorder
  Anxiety disorder
  Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
  
  s such as obsessive-compulsive disorder
  Obsessive-compulsive disorder
  Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
  
   (OCD) and social phobia
  Social anxiety disorder
  Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
  
  , with or without agoraphobia
  Agoraphobia
  Agoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...
  
  ).
• Although not FDA approved for the indication, it is sometimes used off-label
  Off-label use
  Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
  
   for augmentation of selective serotonin reuptake inhibitor
  Selective serotonin reuptake inhibitor
  Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
  
   (SSRI) therapy against depression
  Clinical depression
  Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
  
  .

Adverse effects

• Common: dizziness, nausea, headache, nervousness, lightheadedness, and excitement.

Contraindications

• Hypersensitivity to buspirone.
• not to be used with MAO inhibitors.
• Severely compromised liver
  Liver
  The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
  
   and/or renal function.
• Asthma
  Asthma
  Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
  
  , history of bronchiospasm or obstructive airways disease.
• Metabolic acidosis
  Metabolic acidosis
  In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
  
  , as in diabetes.

• Epilepsy
• Pre-existing heart conditions
  Heart disease
  Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
  
   (e.g., myocardial infarction
  Myocardial infarction
  Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
  
  )
• Acute, closed-angle glaucoma
• Myasthenia gravis
  Myasthenia gravis
  Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
  
  

Interactions

Inhibitors and Inducers of Cytochrome P450 3A4 (CYP3A4): Buspirone has been shown in vitro to be metabolized by CYP3A4. This finding is consistent with the in vivo interactions observed between Buspirone and the following

• Itraconazole
  Itraconazole
  Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
  
  : Increased plasma level of buspirone.
• Nefazodone
  Nefazodone
  Nefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...
  
  : Increased plasma levels of buspirone.
• Rifampicin
  Rifampicin
  Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
  
  : Decreased plasma levels of buspirone.
• Carbamazepine
  Carbamazepine
  Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
  
  : Reduced plasma levels of buspirone.
• Haloperidol
  Haloperidol
  Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
  
  : Increased plasma levels of haloperidol.
• Grapefruit or grapefruit juice
  Grapefruit
  The grapefruit , is a subtropical citrus tree known for its sour fruit, an 18th-century hybrid first bred in Barbados. When found, it was named the "forbidden fruit"; it has also been misidentified with the pomelo or shaddock , one of the parents of this hybrid, the other being sweet orange The...
  
  : Significantly increases the plasma levels of buspirone. The probable mechanism of this interaction caused by grapefruit juice is delayed gastric emptying and inhibition of the cytochrome P450 3A4-mediated first-pass metabolism of buspirone.
• other inhibitors or inducers of P450 3A4: accordingly.

MAO inhibitors: There have been reports of the occurrence of elevated blood pressure when Buspirone hydrochloride has been added to a regimen including an MAOI.

Pharmacology

Buspirone functions as a serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 5-HT_1A receptor

5-HT1A receptor

The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

 partial agonist

Partial agonist

Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...

. It is this action that is thought to mediate its anxiolytic and antidepressant effects. Additionally, it functions as a dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 D₂, as well as α₁, and α₂-adrenergic receptor antagonist

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

to a lesser degree, though these properties are generally undesirable in an anxiolytic and likely only contribute to side effects.

Research

• In a 1996 study buspirone has been investigated and found useful as an adjoint treatment for alcohol dependence
  Alcoholism
  Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
  
  
• Although not related to clinical indications, it is interesting that in a study in rats buspirone has been found to improve spatial learning and memory
  Spatial memory
  In cognitive psychology and neuroscience, spatial memory is the part of memory responsible for recording information about one's environment and its spatial orientation. For example, a person's spatial memory is required in order to navigate around a familiar city, just as a rat's spatial memory is...
  
   after traumatic brain injury
  Traumatic brain injury
  Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
  
   (TBI). Such findings may have clinical relevance to TBI patients.

Comparison to benzodiazepines

Buspirone's chemical structure

Chemical structure

A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...

 and mechanism of action

Mechanism of action

In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...

 are completely unrelated to those of the benzodiazepine

Benzodiazepine

A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

s, and its efficacy

Efficacy

Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...

 is not comparable to that of members of the benzodiazepine family in treating GAD.

Buspirone shows no potential for addiction or dependence

Physical dependence

Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...

, and the development of tolerance has not been observed. Furthermore, cross-tolerance

Cross-tolerance

Cross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to...

 to benzodiazepines, barbiturate

Barbiturate

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...

s, and alcohol

Ethanol

Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, as well as other GABAergics, is not present either.It may take several weeks before its anxiolytic effects become noticeable. Many patients may also require a higher dosage to adequately respond to treatment.

In a study of diazepam and buspirone in GAD patients both drugs were effective, but buspirone took longer to take effect. Abrupt discontinuation after 6 weeks resulted in withdrawal symptoms in diazepam, which were not present with buspirone. This indicated a risk of physical dependence with diazepam, which is not present with buspirone.

Buspirone is ineffective for benzodiazepine withdrawal, does not improve discontinuation rates and does not decrease the severity of withdrawal symptoms.

Chemistry

The synthesis of buspirone starts with the N-alkylation of 1-(2-pyrimidyl)piperazine with 4-chlorobutyronitrile followed by hydrogenation

Hydrogenation

Hydrogenation, to treat with hydrogen, also a form of chemical reduction, is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically...

 of the nitrile

Nitrile

A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

 over Raney nickel

Raney nickel

Raney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...

 catalyst. The primary amine product of the previous step is reacted with the depicted spirocyclic acid anhydride to yield buspirone.