Buspirone

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


width = 93
CAS_number = 36505-84-7
ChemSpiderID = 2383
ATC_prefix = N05
ATC_suffix = BE01
ATC_supplemental =
PubChem = 2477
DrugBank = APRD00222
C=21|H=31|N=5|O=2
molecular_weight = 385.50314 g/mol
bioavailability = low and variable (approx. 5%), due to high first pass metabolism
protein_bound = 95% bound to plasma proteins
metabolism = mainly hepatic, active metabolite 1-Pyrimidylpiperazin (1-PP)
elimination_half-life = 2-3hr
pregnancy_US = B
pregnancy_category =
legal_status = Rx-only, not a controlled substance
routes_of_administration = oral
excretion = urine (29-63%) and feces (18-38%) in the form of metabolites

Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Buspisal, Narol, Spitomin, Sorbon) is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam in treating generalized anxiety disorder. [cite journal |last=Cohn |first=JB |coauthors=Rickels K |year=1989 |title=A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety |journal=Curr Med Res Opin. |volume=11 |issue=5 |pages=304–320 ] [cite journal |last=Goldberg |first=HL |coauthors=Finnerty RJ |year=1979 |month=September |title=The comparative efficacy of buspirone and diazepam in the treatment of anxiety |journal=Am J Psychiatry |volume=136 |issue=9 |pages=1184–1187 ]

It shows no potential for addiction compared to other drugs commonly prescribed for anxiety, especially benzodiazepine medications. The development of tolerance has not been noticed. Cross-tolerance to benzodiazepines, barbiturates and alcohol does not exist. Furthermore, it is non-sedating.

It is thought to act by interfering with the function of the neurotransmitter serotonin in the brain, particularly by serving as a 5-HT1A presynaptic receptor partial agonist. Additionally, it acts as a mixed agonist/antagonist on postsynaptic dopamine receptors. GABA-mediated effects are lacking. Buspirone may also have indirect effects on other neurotransmitters in the brain.

The action of a single dose is much longer than the short half-life of 2-3 hours indicates. The bioavailability of buspirone is very low and variable due to extensive first pass metabolism. The drug is quickly resorbed. Taking the drug together with food may increase the bioavailability. The drug is highly (95%) plasma-bound. The active metabolite 1-PP is also a 5-HT1A partial agonist with anxiolytic properties, but weaker so than the mother-drug.

It is also useful as an augmenting agent, for the treatment of depression, when added to SSRIs.

The main disadvantage is 1 to 3 weeks elapse before the anxiolytic activity becomes evident. Often patients have to be initially cotreated with a benzodiazepine for immediate anxiolysis. Generally, buspirone is less effective than benzodiazepines. Therefore, benzodiazepines are often the first approach in immediately treating panic attacks and social phobias. It is also particularly difficult to treat patients pretreated with benzodiazepines, for they now know the immediate effects of these anxiolytics and may not think buspirone is providing them with the same level of relief.

Bristol-Myers Squibb gained FDA approval for Buspirone in 1986. The drug went generic in 2001.

Indications

* Generalized anxiety disorder of mild to moderate intensity (it is not considered effective against other types of anxiety disorders such as obsessive-compulsive disorder, with or without agoraphobia and social phobia)
* Augmentation of SSRI-treatment against depression
* Attention-Deficit Hyperactivity Disorder (ADHD)
* In experimental trials with rats, busprione has been shown to improve spatial learning and memory after traumatic brain injury (TBI). Such findings may have clinical relevance to TBI patients. [Kline, Anthony, E., Olsen, Adam, S., Zafonte, Ross D., Sozda, Christopher N., Aslam, Haris, A., and Cheng, Jeffrey P. (September 2007). "Brain injury delayed and chronic buspirone treatment after experimental traumatic brain injury enhances spatial acquisition". "Archives of Physical Medicine and Rehablitation." 88 (9): E6.]

Contraindications

* Myasthenia gravis
* Acute closed angle glaucoma
* Severely compromised liver- and renal-function
* Concomitant treatment with a MAO-Inhibitor (severe hypertensive crises have been seen)
* Preexisting heart conditions (e.g. myocardial infarction)

Side-effects

Rarely, side-effects have a dangerous nature or intensity. Some tend to disappear with continued therapy, or are less frequent if the initial dose is low and increased gradually (vertigo, agitation, insomnia).

* Most frequent: vertigo, headaches, nervousness, agitation, light-headedness, nausea;
* Often (>1%) : drowsiness, insomnia, concentration disorders, confusion, depression, agitation, intestinal disorders, paresthesia, coordination disorders, tremors, disturbed vision, tinnitus, fatigue, weakness, Angina pectoris, sore throat, tachycardias, palpitations, dry mouth, pain in muscles and joints;
* Seldom: allergic reactions, subdermal bleeding, extrapyramidal symptoms, hallucinations, psychosis, ataxia, epileptic seizures, syncope, tunnel vision, urine retention, hyperosmia, alopecia, pruritus, hot flashes.

There are no dyscognitive side-effects like those seen in benzodiazepines.

Other side-effects have been seen, but are not more frequent than those encountered with placebo. An unusual side effect reported by patients has been an enhanced sense of smell.

Drug abuse and dependence

Buspirone has no known potential for abuse, psychological or physical dependence. [cite journal | last = Lydiurd | first = R. Bruce | title = An Overview of Generalized Anxiety Disorder: Disease State-Appropriate Therapy | journal = Clinical Therapeutics | volume = 22 | issue = Supplement A | pages = A3–A24 | year = 2000 | doi = 10.1016/S0149-2918(00)89070-0]

Interactions

* Haloperidol : increased plasma-levels of haloperidol
* Rifampicin : decreased plasma-levels of buspirone
* MAO-Inhibitors : severe hypertensive crises are possible.
* Alcohol : The sedative properties of alcohol are increased slightly.
* Grapefruit, Grapefruit juice, Grapefruit extract : drastically increased plasma-levels of Buspirone [cite journal |last=Lilja |first=JJ |coauthors=Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ |year=1998 |month=December |title=Grapefruit juice substantially increases plasma concentrations of buspirone |journal=Clinical Pharmacology & Therapeutics |volume=64 |issue=6 |pages=655–660 ] Do not mix the pills in grapefruit juice.

References