Buspirone
From Wikipedia, the free encyclopedia
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Buspirone
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| Systematic (IUPAC) name | |
| 8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]- 8-azaspiro[4.5]decane-7,9-dione |
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| Identifiers | |
| CAS number | |
| ATC code | N05 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C21H31N5O2 |
| Mol. mass | 385.50314 g/mol |
| Pharmacokinetic data | |
| Bioavailability | low and variable (approx. 5%), due to high first pass metabolism |
| Protein binding | 95% bound to plasma proteins |
| Metabolism | mainly hepatic, active metabolite 1-Pyrimidylpiperazin (1-PP) |
| Half life | 2-3hr |
| Excretion | urine (29-63%) and feces (18-38%) in the form of metabolites |
| Therapeutic considerations | |
| Pregnancy cat. |
B(US) |
| Legal status |
Rx-only, not a controlled substance |
| Routes | oral |
Buspirone (sold as Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Buspisal, Narol, Spamilan, Spitomin, Sorbon) is a psychoactive drug and member of the azapirone chemical class that is used primarily as an anxiolytic, but also as an antidepressant. It functions as a serotonin 5-HT1A receptor partial agonist. Bristol-Myers Squibb gained FDA approval for buspirone in 1986 and it went generic in 2001.
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[edit] Indications
- Generalized anxiety disorder (GAD) of mild to moderate intensity (it is not considered effective against other types of anxiety disorders such as obsessive-compulsive disorder (OCD), with or without agoraphobia and social phobia).
- Augmentation of selective serotonin reuptake inhibitor (SSRI) therapy against depression or anxiety.
- In experimental trials with rats, buspirone has been shown to improve spatial learning and memory after traumatic brain injury (TBI). Such findings may have clinical relevance to TBI patients.[1]
[edit] Comparison to benzodiazepines
Buspirone's chemical structure and mechanism of action are completely unrelated to those of the benzodiazepines, but it purportedly has an efficacy comparable to diazepam (Valium) in treating generalized anxiety disorder.[2][3] Unlike the benzodiazepines, buspirone shows no potential for addiction or dependence, and the development of tolerance has not been observed. Furthermore, cross-tolerance to benzodiazepines, barbiturates, and alcohol, as well as other GABAergics, is not present either. Additionally, it is non-sedating, non-cognitive/memory impairing, and has a generally very favorable side effect profile.
The main disadvantage of buspirone is that it may take several weeks before its anxiolytic effects become noticeable. Many patients may also require a higher dosage to adequately respond to treatment, which may also be increased in slow increments of 5 mg every three days and up to 60 mg a day, which may be the dose required for adequate relief. This makes it particularly difficult to treat patients pre-treated with benzodiazepines, for they know the immediate effects of these anxiolytics. Often patients have to be initially co-treated with a benzodiazepine for an immediate anxiolytic effect.
Therefore, benzodiazepines are often the first approach in treating acute panic attacks and social phobias. Although buspirone may be a consideration for patients whose benzodiazepine therapy is becoming extensive beyond weeks, buspirone must not be assumed to counteract the withdrawal effects of benzodiazepines, which in severe chronic high-dose cases, can include seizures, coma and death.
Benzodiazepines should be gradually withdrawn, for example Xanax may safely be withdrawn by 0.25 mg every two weeks in some patients who’ve been taking large chronic doses[citation needed]. As the mechanism of action in the brain between benzodiazepines which modulate GABA receptors and buspirone which antagonises the serotonin receptors is uncorrelated, it is essential that buspirone is not considered an anxiolytic agent which may shorten the benzodiazepine withdrawal period or help prevent or lessen the severity of benzodiazepine withdrawal symptoms.
[edit] Pharmacology
Buspirone functions as a serotonin 5-HT1A receptor partial agonist.[4] It is this action that is thought to mediate its anxiolytic and antidepressant effects. Additionally, it functions as a dopamine D2, and α1/α2-adrenergic receptor antagonist to a lesser degree, though these properties are generally undesirable and probably only contribute to side effects.
[edit] Pharmacokinetics
The action of a single dose is much longer than the short half-life of 2–3 hours indicates.[citation needed] 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 parent compound.
[edit] 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 reaction, subdermal bleeding, extrapyramidal symptoms, hallucinations, psychosis, ataxia, epileptic seizures, syncope, tunnel vision, urinary retention, hyperosmia, alopecia, pruritus, hot flashes.
Other side-effects have been seen, but are not more frequent than those encountered with placebo. An unusual side effect reported by patients is an enhanced sense of smell.
[edit] Interactions
- Haloperidol: Increased plasma-levels of haloperidol.
- Rifampicin: Decreased plasma-levels of buspirone.
- Alcohol: The sedative properties of alcohol are increased slightly.[citation needed]
- Grapefruit, grapefruit juice, grapefruit extract: Drastically increased plasma levels of buspirone.[5] Excessive quantities of grapefruit juice should be avoided.
[edit] Contraindications
- Myasthenia gravis
- Acute closed angle glaucoma
- Severely compromised liver- and renal-function
- Preexisting heart conditions (e.g. myocardial infarction)
[edit] Abuse and dependence
Buspirone has no known potential for abuse, psychological or physical dependence.[6]
[edit] References
- ^ 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 Rehabilitation. 88 (9): E6.
- ^ Cohn, JB; Rickels K (1989). "A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety". Curr Med Res Opin. 11 (5): 304–320.
- ^ Goldberg, HL; Finnerty RJ (September 1979). "The comparative efficacy of buspirone and diazepam in the treatment of anxiety". Am J Psychiatry 136 (9): 1184–1187.
- ^ Bller P (May 1997). "'Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response.'". Neuropsychopharmacology (5). http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=9109104&ordinalpos=19&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum.
- ^ Lilja, JJ; Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ (December 1998). "Grapefruit juice substantially increases plasma concentrations of buspirone". Clinical Pharmacology & Therapeutics 64 (6): 655–660. doi:.
- ^ Lydiurd, R. Bruce (2000). "An Overview of Generalized Anxiety Disorder: Disease State-Appropriate Therapy". Clinical Therapeutics 22 (Supplement A): A3–A24. doi:.
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