Buspirone
From Wikipedia, the free encyclopedia
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| Systematic (IUPAC) name | |
| 8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione | |
| Clinical data | |
| Trade names | Buspar |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a688005 |
| Pregnancy cat. | B(US) |
| Legal status | ℞ Prescription only |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 5% |
| Protein binding | 95% |
| Metabolism | Hepatic |
| Half-life | 2-3 hours |
| Excretion | Urine (29-63%), Feces (18-38%) |
| Identifiers | |
| CAS number | 36505-84-7  |
| ATC code | N05BE01 |
| PubChem | CID 2477 |
| IUPHAR ligand | 36 |
| DrugBank | APRD00222 |
| ChemSpider | 2383 |
| UNII | TK65WKS8HL |
| KEGG | D07593 |
| ChEBI | CHEBI:3223 |
| ChEMBL | CHEMBL49 |
| Chemical data | |
| Formula | C21H31N5O2 |
| Mol. mass | 385.50314 g/mol |
| SMILES | eMolecules & PubChem |
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Buspirone (pronounced byoo-spur-own (trade name Buspar, pronounced byoo-spar) is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder (GAD)
Bristol-Myers Squibb (BMS) gained FDA approval 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.
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[edit] Medical uses
- Generalized anxiety disorder (GAD) of very mild to moderate intensity, without any panic attacks (it is not generally considered to be effective, nor does it have regulatory approval for other types of anxiety disorders such as obsessive-compulsive disorder (OCD) and social phobia, with or without agoraphobia).[1]
- Although not FDA approved for the indication, it is sometimes used off-label for augmentation of selective serotonin reuptake inhibitor (SSRI) therapy against depression.[citation needed]
[edit] Adverse effects
- Common: dizziness, nausea, headache, nervousness, lightheadedness, and excitement.[1]
[edit] Contraindications
- Hypersensitivity to buspirone.[1]
- not to be used with MAO inhibitors.[1]
- Severely compromised liver and/or renal function.[1]
- Asthma, history of bronchiospasm or obstructive airways disease.[2]
- Metabolic acidosis, as in diabetes.[2]
- Epilepsy[citation needed]
- Pre-existing heart conditions (e.g., myocardial infarction)[citation needed]
- Acute, closed-angle glaucoma[citation needed]
- Myasthenia gravis[citation needed]
[edit] 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: Increased plasma level of buspirone.[1]
- Nefazodone: Increased plasma levels of buspirone.[1]
- Rifampicin: Decreased plasma levels of buspirone.[1]
- Carbamazepine: Reduced plasma levels of buspirone.[1]
- Haloperidol: Increased plasma levels of haloperidol.[1]
- Grapefruit or grapefruit juice: 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.[3][1]
- other inhibitors or inducers of P450 3A4: accordingly.[1]
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.[1]
[edit] Pharmacology
Buspirone functions as a serotonin 5-HT1A receptor partial agonist.[4][1] It is this action that is thought to mediate its anxiolytic and antidepressant effects. Additionally, it functions as a dopamine D2[1], as well as α1, and α2-adrenergic receptor antagonist[citation needed] to a lesser degree, though these properties are generally undesirable in an anxiolytic and likely only contribute to side effects.[citation needed]
[edit] Research
- In a 1996 study buspirone has been investigated and found useful as an adjoint treatment for alcohol dependence[5]
- 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 after traumatic brain injury (TBI). Such findings may have clinical relevance to TBI patients.[6]
[edit] Comparison to benzodiazepines
Buspirone's chemical structure and mechanism of action are completely unrelated to those of the benzodiazepines, and its efficacy is not comparable to that of members of the benzodiazepine family in treating GAD.[7][8]
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. It may take several weeks before its anxiolytic effects become noticeable. Many patients may also require a higher dosage to adequately respond to treatment.[1]
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.[9]
Buspirone is ineffective for benzodiazepine withdrawal, does not improve discontinuation rates and does not decrease the severity of withdrawal symptoms.[10]
[edit] Chemistry
The synthesis of buspirone starts with the N-alkylation of 1-(2-pyrimidyl)piperazine with 4-chlorobutyronitrile followed by hydrogenation of the nitrile over Raney nickel catalyst. The primary amine product of the previous step is reacted with the depicted spirocyclic acid anhydride to yield buspirone.[11]
[edit] See also
[edit] References
- ^ a b c d e f g h i j k l m n o p "Buspirone monograph". Drugs.com. http://www.drugs.com/pro/buspirone.html. Retrieved 2011-08-27.
- ^ a b Geddes, John; Gelder, Michael G.; Mayou, Richard (2005). Psychiatry. Oxford [Oxfordshire]: Oxford University Press. p. 237. ISBN 0-19-852863-9.
- ^ Lilja, J. J.; Kivistö, K. T.; Backman, J. T.; Lamberg, T. S.; Neuvonen, P. J. (1998). "Grapefruit juice substantially increases plasma concentrations of buspirone*". Clinical Pharmacology & Therapeutics 64 (6): 655–660. doi:10.1016/S0009-9236(98)90056-X. PMID 9871430.
- ^ Blier, P.; Bergeron, R.; De Montigny, C. (1997). "Selective Activation of Postsynaptic 5-HT1A Receptors Induces Rapid Antidepressant Response". Neuropsychopharmacology 16 (5): 333–338. doi:10.1016/S0893-133X(96)00242-4. PMID 9109104.
- ^ Malec, T. S.; Malec, E. A.; Dongier, M. (1996). "Efficacy of buspirone in alcohol dependence: A review". Alcoholism, clinical and experimental research 20 (5): 853–858. doi:10.1111/j.1530-0277.1996.tb05263.x. PMID 8865960.
- ^ Cheng, J. P.; Hoffman, A. N.; Zafonte, R. D.; Kline, A. E. (2008). "A delayed and chronic treatment regimen with the 5-HT1A receptor agonist 8-OH-DPAT after cortical impact injury facilitates motor recovery and acquisition of spatial learning". Behavioural Brain Research 194 (1): 79–85. doi:10.1016/j.bbr.2008.06.025. PMC 2568997. PMID 18638506. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2568997.
- ^ Cohn, J. B.; Rickels, K.; Steege, J. F. (1989). "A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety". Current Medical Research and Opinion 11 (5): 304–320. doi:10.1185/03007998909115213. PMID 2649317.
- ^ Goldberg, H. L.; Finnerty, R. J. (1979). "The comparative efficacy of buspirone and diazepam in the treatment of anxiety". The American journal of psychiatry 136 (9): 1184–1187. PMID 382878.
- ^ Murphy, S. M.; Owen, R.; Tyrer, P. (1989). "Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks' treatment with diazepam or buspirone". The British journal of psychiatry : the journal of mental science 154: 529–534. doi:10.1192/bjp.154.4.529. PMID 2686797.
- ^ Sontheimer, D. L.; Ables, A. Z. (2001). "Is imipramine or buspirone treatment effective in patients wishing to discontinue long-term benzodiazepine use?". The Journal of family practice 50 (3): 203. PMID 11252203.
- ^ Wu, Y. H.; Rayburn, J. W.; Allen, L. E.; Ferguson, H. C.; Kissel, J. W. (1972). "Psychosedative agents. 2. 8-(4-Substituted 1-piperazinylalkyl)-8-azaspiro[4.5]decane-7,9-diones". Journal of Medicinal Chemistry 15 (5): 477. doi:10.1021/jm00275a009. PMID 5035267. ;
DE 2057845, Rayburn JW, Wu YH, "Heterocyclische Azaspirodecandione und Verfahren zu ihrer Herstellung", published 1971-06-09;
US 3717634, Rayburn JW, Wu YH, "N-(heteroarcyclic)piperazinylalkyl-azaspiroalkanediones", published 1973-02-20;
US 3907801, Rayburn JW, Wu YH, "N-{8 (4-pyridyl-piperazino)-alkyl}-9-azaspiroalkanediones", published 1975-09-23;
US 3976776, Rayburn JW, Wu YH, "Tranquilizer process employing N-(heteroarcyclic)piperazinylalkylazaspiroalkanediones", published 1976-08-24
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