Buspirone , sold under the brand name Buspar , is an anxiolytic drug that is primarily used to treat generalized anxiety disorders (GAD). It is also commonly used to supplement antidepressants in the treatment of major depressive disorders. Unlike most anxiolytics, the pharmacology of buspirone is not associated with benzodiazepines, barbiturates, or carbamates (it is not a GABA receptor agonist), and so buspirone carries no risk of physical dependence and withdrawal symptoms to which these drug classes are known. Buspirone is not considered a drug abuse, safer in overdose than traditional anxiolytics, and significantly less damaging to therapeutic doses.
Video Buspirone
Medical use
Anxiety
Buspirone is approved in the United States by the Food and Drug Administration (FDA) for the treatment of short or long-term anxiety disorders or can also be used to relieve short-term anxiety symptoms. Similarly in Australia, buspirone is licensed for the treatment of anxiety disorders. In the UK, the buspirone is only indicated for the treatment of short-term anxiety.
Buspirone has no immediate anxiolytic effect, and hence has a delayed onset of action; full clinical effectiveness may take 2 to 4 weeks to manifest. This drug proved to be equally effective in the treatment of GAD for benzodiazepines including diazepam, alprazolam, lorazepam, and clorazepate. Buspirone is not known to be effective in the treatment of anxiety disorders other than GAD, although there is some limited evidence that may be useful in the treatment of social phobia in addition to selective serotonin reuptake inhibitors (SSRIs).
Depression
Although not approved for this indication, studies such as STAR * D have shown buspirone to be an effective augmentation agent in addition to treatment with selective serotonin reuptake inhibitors (SSRIs) for clinical depression and are also used to counter sexual dysfunction (anorgasmia and erectile dysfunction) associated with SSRIs. The drug is also found to be effective in the treatment of depression as a stand-alone drug.
Other uses
Cerebellar ataxia
There is evidence that buspirone can be used to treat cerebellar ataxia.
Sexual dysfunction
There is some evidence that the buspirone itself may be useful in the treatment of hypoactive sexual desire disorder (HSDD) in women.
ADHD
Several clinical trials, mostly randomized double-blind trials (and in one buspirone used in addition to atomoxetine) and one open label, have been performed to evaluate the usefulness of buspirone in the treatment of attention deficit hyperactivity disorder (ADHD), with most positive results.
Miscellaneous
Buspirone may be useful in the management of irritability, agitation, and aggression in older patients with dementia and pediatrics, although further research is needed to more clearly establish its effectiveness.
Buspirone is ineffective as a treatment for withdrawal of benzodiazepine, withdrawal of barbiturates, or withdrawal of alcohol/tremor delirium.
Maps Buspirone
Contraindications
Buspirone has this contraindication:
- Hypersensitivity to buspirone
- Metabolic acidosis, as in diabetes
- Should not be used with MAO inhibitor
- Heavily impaired liver and/or kidney function
Side effects
Known side effects associated with buspirone include dizziness, headache, nausea, anxiety, and paresthesia. Buspirone is relatively well tolerated, and is not associated with sedation, cognitive and psychomotor disorders, muscle relaxation, physical dependence, or anticonvulsant effects. In addition, the buspirone does not produce euphoria, and is not a drug of abuse.
Overdose
Buspirone seems relatively benign in the case of a single drug overdose, although no exact data on this subject appears to be available. In one clinical trial, buspirone was administered to healthy male volunteers at a dose of 375 mg/d, and resulted in side effects including nausea, vomiting, dizziness, drowsiness, miosis, and gastric disorders. In early clinical trials, buspirone was administered at doses of even 2,400 mg/day, with akathisia, tremor, and muscle stiffness being observed. A deliberate overdose with 250 mg and up to 300 mg of buspirone has caused drowsiness in about 50% of individuals. One death has been reported to be associated with 450mg of buspirone along with alprazolam, diltiazem, alcohol, cocaine.
Interactions
Buspirone has been shown to be in vitro metabolized by the CYP3A4 enzyme. These findings are consistent with the in vivo interactions observed between this buspirone and inhibitor or the cytochrome P450 3A4 inducer (CYP3A4), including:
- Itraconazole: Increased plasma buspirone
- Rifampicin: Decrease in plasma buspirone
- Nefazodone: Increased plasma buspirone
- Haloperidol: Increased plasma levels of haloperidol
- Carbamazepine: Decreased plasma buspirone
- Grapefruit: Significantly increase plasma buspirone levels. See grapefruit drug interactions.
An increase in blood pressure has been reported when the buspirone has been given to patients taking monoamine oxidase inhibitors (MAOIs).
Pharmacology
Pharmacodynamics
Buspirone acts as a 5-HT serotonin receptor agonist 1A with high affinity. This is a presynaptic 5-HT receptor agonist 1A , which is an inhibitor of autoreceptors, and partial agonists of 5-HT postsynaptic receptors 1A . Similarly, a study in animals found that the buspirone-dependent dose decreased serotonin levels in certain brain areas while increasing dopamine and norepinephrine levels. It is thought that the main effects of buspirone are mediated through their interaction with 5-HT receptors 1A . Some of the effects may be mediated through secondary oxytocin release to the 5-HT receptor agonist 1A . Buspirone also has a lower affinity for serotonin 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT 6 , and 5-HT 7 receptors.
In addition to binding to the serotonin receptor, the buspirone is the antagonist of the dopamine D 2 receptor with a weak affinity. It is preferred to block the presinaptic receptors D 2 autoreceptors, and postsynaptic receptor antagonists D 2 only at higher doses. Accordingly, buspirone has been found to increase dopaminergic neurotransmission in the low-dose nigrostriatal pathway, whereas at higher doses, postsynaptic receptors D 2 are blocked and antidopaminergic effects such as hypoactivity and reduced stereotypes, though not catalepsy, are observed in animal. Buspirone has also been found to bind with a much higher affinity to dopamine D 3 and D 4 receptors, where it is also an antagonist.
The main metabolite of buspirone, 1- (2-pyrimidinyl) piperazine (1-PP), occurs at a higher circulation rate than the buspirone itself, and is known to act as a strong receptor antagonist? 2 -adrenergik. It may be responsible for the increase in noradrenergic and dopaminergic activity observed with buspirone in animals. In addition, 1-PP can play an important role in the antidepressant effect of buspirone. Buspirone also has a very weak affinity and may be clinically unimportant for adrenergic receptors? 1 . However, buspirone has been reported to have shown "significant and selective intrinsic efficacy" in adrenergic receptors? 1 expressed in "network and how to depend on species".
Unlike benzodiazepines, buspirone does not interact with the GABA receptor complex A .
Pharmacokinetics
Buspirone has a low oral bioavailability of 3.9% relative to intravenous injection because of its wide first-pass metabolism. The time to reach the plasma level after consumption is 0.9 to 1.5 hours. It is reported to have a 2.8 hour elimination half, although a review of 14 studies found that the average half-life of the terminal ranged between 2 and 11 hours, and one study even reported a terminal half-life of 33 hours. Buspirone is metabolized mainly by CYP3A4, and prominent drug interactions with these enzyme inhibitors and inducers have been observed. The main metabolism of buspirone includes 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-PP. 6-Hydroxybuspirone has been identified as a major liver metabolite of buspirone, with plasma levels being 40-fold greater than that of buspirone after oral administration of buspirone to humans. Metabolites are high-affinity partial agonists of the 5-HT recipes 1A (K i = 25Ã, nM) the same as buspirone, and have shown occupancy of 5-HT 1A receptors in vivo . Thus, it is likely to play an important role in the therapeutic effect of buspirone. 1-PP has also been found to be circulating at a higher rate than the buspirone itself and may also play an important role in the clinical effects of buspirone.
Chemistry
Buspirone is a member of the chemical class of azapirone, and consists of azaspirodecanedione and pyrimidinylpiperazine components that are linked together by butyl chains.
Analogy
The structural analogues of buspirone include other azapiron such as gepirone, ipsapirone, perospirone, and tandospirone.
Synthesis
Alkylation 1 - (2-pyrimidyl) piperazine ( 1 ) with 3-chloro-1-cyanopropane ( 2 , 4-chlorobutyronitrile) gives 3 , which is reduced either by hydrogenation through Raney nickel catalyst, or by LAH. The 1 Â ° amine ( 4 ) of the previous step is then reacted with 3,3-tetramethyleneglutaric anhydride ( 5 , 8-Oxaspiro [4,5] decane-7,9 -dione) to generate buspirone ( 6 ).
History
Buspirone was first synthesized, by the team at Mead Johnson, in 1968, but was not patented until 1975. It was originally developed as an antipsychotic drug acting on D 2 substitutes, but was found ineffective. in the treatment of psychosis and diverted as anxiolytic. In 1986, Bristol-Myers Squibb obtained FDA approval for buspirone in the treatment of GAD. The patents placed on the buspirone expired in 2001 and are now available as generics.
Society and culture
Common names
Buspirone is INN , BAN , DCF , and DCIT of buspirone, while buspirone hydrochloride is USAN , BANM , and JAN .
Brand name
Buspirone is mainly sold under the brand Buspar.
Research
Female sexual dysfunction
Buspirone/testosterone (brand name while Lybridos) is a combination of buspirone and testosterone formulations that are being developed by a pharmaceutical company called Emotional Brain for the treatment of female sexual dysfunction.
References
Source of the article : Wikipedia
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