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Additional information about the drug Buspirone


Buspirone, sold under the brand name Buspar, is an anxiolytic drug that is primarily used to treat generalized anxiety disorder (GAD). Unlike most anxiolytics, the pharmacology of buspirone is not related to that of benzodiazepines, barbiturates, or carbamates (it is not a GABA receptor analog ), and so buspirone does not carry the risk of physical dependence and withdrawal symptoms for which those drug classes are known. Buspirone is not considered to be a drug-of-abuse, is safer in overdose than traditional anxiolytics, and is significantly less impairing at therapeutic doses.
Contents
1 Medical uses
1.1 Anxiety
1.2 Depression
1.3 Other uses
1.3.1 Cerebellar ataxia
1.3.2 Sexual dysfunction
1.3.3 ADHD
1.3.4 Miscellaneous
2 Contraindications
3 Side effects
4 Overdose
5 Interactions
6 Pharmacology
6.1 Pharmacodynamics
6.2 Pharmacokinetics
7 Chemistry
7.1 Analogues
7.2 Synthesis
8 History
9 Society and culture
9.1 Generic names
9.2 Brand name
10 Research
10.1 Female sexual dysfunction
11 References
Medical uses
Anxiety
Buspirone is approved in the United States by the Food and Drug Administration (FDA) for the short- or long-term treatment of anxiety disorders or can also be used for the short-term relief of the symptoms of anxiety.
Buspirone has no immediate anxiolytic effects, and hence has a delayed onset of action ; its full clinical effectiveness may require 2 to 4 weeks to manifest.
Depression
Although not approved for this indication, studies such as STAR*D have shown buspirone to be an effective augmentation agent alongside treatment with selective serotonin reuptake inhibitors (SSRIs) for clinical depression and is also used to counter the sexual dysfunction ( anorgasmia and erectile dysfunction ) associated with SSRIs.
Other uses
Cerebellar ataxia
There is evidence that buspirone may be used to treat cerebellar ataxia.
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.
ADHD
Several clinical trials, most randomized double-blind trials (and in one buspirone was used as an adjunct to atomoxetine ) and one open-label, have been conducted to evaluate the utility of buspirone in the treatment of attention deficit hyperactivity disorder (ADHD), with mostly positive results.
Miscellaneous
Buspirone may be useful in the management of irritability, agitation, and aggression in older patients with dementia and in pediatrics, although further research is necessary to more clearly establish its effectiveness.
Buspirone is not effective as a treatment for benzodiazepine withdrawal, barbiturate withdrawal, or alcohol withdrawal / delirium tremens.
Contraindications
Buspirone has these contraindications:
Hypersensitivity to buspirone
Metabolic acidosis, as in diabetes
Should not be used with MAO inhibitors
Severely compromised liver and/or kidney function
Side effects
Main article: List of side effects of buspirone
Known side effects associated with buspirone include dizziness, headaches, nausea, nervousness, and paresthesia.
Overdose
Buspirone appears to be relatively benign in cases of single-drug overdose, although no definitive data on this subject appear to be available.
Interactions
Buspirone has been shown in vitro to be metabolized by the enzyme CYP3A4.
Itraconazole : Increased plasma level of buspirone
Rifampicin : Decreased plasma levels of buspirone
Nefazodone : Increased plasma levels of buspirone
Haloperidol : Increased plasma levels of haloperidol
Carbamazepine : Decreased plasma levels of buspirone
Grapefruit: Significantly increases the plasma levels of buspirone. See grapefruit–drug interactions.
Fluvoxamine : 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
Site
K i (nM)
Species
Ref
5-HT 1A
3.98–214 21 (median)
Human
5-HT 1B
>100,000
Rat
5-HT 1D
22,000–42,700
Human
5-HT 2A
138 759–1,300
Human Rat
5-HT 2B
214
Human
5-HT 2C
490 1,100–6,026
Human Rat/pig
5-HT 3
>10,000
Rat
5-HT 4
>10,000
Rat
5-HT 6
398
Mouse
5-HT 7
375–381
Rat
α 1
1,000
Rat
α 2
6,000
Rat
   α 2A
7.3 ( 1-PP )
Human
β
8,800
Rat
D 1
33,000
Rat
D 2
484 240
Human Rat
D 3
98
Human
D 4
29
Human
mACh
38,000
Rat
GABA A ( BDZ )
>100,000
Rat
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site.
Buspirone acts as an agonist of the serotonin 5-HT 1A receptor with high affinity.
In addition to binding to serotonin receptors, buspirone is an antagonist of the dopamine D 2 receptor with weak affinity.
A major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP), occurs at higher circulating levels than buspirone itself, and is known to act as a potent α 2 -adrenergic receptor antagonist.
Unlike benzodiazepines, buspirone does not interact with the GABA A receptor complex.
Pharmacokinetics
Buspirone has a low oral bioavailability of 3.9% relative to intravenous injection due to extensive first-pass metabolism.
Phase I Metabolism of buspirone in humans.
Chemistry
Buspirone is a member of the azapirone chemical class, and consists of azaspirodecanedione and pyrimidinylpiperazine components linked together by a butyl chain.
Analogues
Structural analogues of buspirone include other azapirones like gepirone, ipsapirone, perospirone, and tandospirone.
Synthesis
Buspirone synthesis: DE 2057845   U.S. Patent 3,717,634 U.S. Patent 3,907,801 U.S. Patent 3,976,776
Alkylation of 1-(2-pyrimidyl)piperazine ( 1 ) with 3-chloro-1-cyanopropane ( 2, 4-chlorobutyronitrile) gives 3, which is reduced either by hydrogenation over Raney nickel catalyst, or with LAH. The resulting 1° amine ( 4 ) from the previous step is then reacted with 3,3-tetramethyleneglutaric anhydride ( 5, 8-Oxaspiro[4.5]decane-7,9-dione) in order to yield buspirone ( 6 ).
History
Buspirone was first synthesized, by a team at Mead Johnson, in 1968, The patent placed on buspirone expired in 2001 and it is now available as a generic drug.
Society and culture
Buspar (buspirone) 10-mg tablets.
Generic names
Buspirone is the INN, BAN, DCF, and DCIT of buspirone, while buspirone hydrochloride is its USAN, BANM, and JAN.
Brand name
Buspirone is primarily sold under the brand name Buspar.
Research
Female sexual dysfunction
Buspirone/testosterone (tentative brand name Lybridos) is a combination formulation of buspirone and testosterone which is under development by a pharmaceutical company called Emotional Brain for the treatment of female sexual dysfunction.

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