Wikipedia - Nefazodone
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Nefazodone
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| Systematic (IUPAC) name | |
| 1-(3-[4-(3-chlorophenyl)piperazin-1-yl]propyl)-3-ethyl-4-(2-phenoxyethyl)-1H-1,2,4-triazol-5(4H)-one | |
| Identifiers | |
| CAS number | 83366-66-9 |
| ATC code | N06AX06 |
| PubChem | 4449 |
| DrugBank | APRD00402 |
| ChemSpider | 4294 |
| Chemical data | |
| Formula | C25H32ClN5O2 |
| Mol. mass | 470.01 g/mol |
| Physical data | |
| Melt. point | 83–84 °C (181–183 °F) |
| Pharmacokinetic data | |
| Bioavailability | 20% (variable) |
| Protein binding | >99% |
| Metabolism | Hepatic (active metabolites, including mCPP)[1] |
| Half life | 2–4 hours |
| Excretion | In urine (55%) and feces (20–30%) |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status |
? Prescription only |
| Routes | Oral |
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Nefazodone (sold as Serzone, Nefadar) is a psychoactive drug and antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity (liver damage), which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years.[2] On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States and Canada. Several generic formulations of nefazodone are still available.[3][4]
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[edit] Pharmacology
Nefazodone acts primarily as a potent antagonist at the 5-HT2 receptors (26 nM).[5] It also has moderate affinity for the a1-adrenergic receptor (48 nM) and 5-HT1A receptor (80 nM), and very low affinity for the a2-adrenergic receptor (640 nM) and D2 receptor (910 nM).[5] It acts as an antagonist at all of these sites.[5][6] Nefazodone has low affinity for the serotonin (200 nM), norepinephrine (360 nM), and dopamine (360 nM) transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).[7] It has negligible affinity for the H1 receptor (24,000 nM) or muscarinic acetylcholine receptors (11,000 nM), and accordingly lacks any antihistamine or anticholinergic side effects.[7]
[edit] Dosing
Nefazodone doses for adults typically start at 50 mg twice daily uptitrated by 100 mg/day per week to a maximum of 600 mg (300 mg twice daily), according to Food and Drug Administration (FDA) regulations. Some patients with severe depression were treated with more than 600 mg/day. Most patients were treated with 300 mg–600 mg daily.
[edit] Side effects
Unlike most serotonin reuptake inhibitors, Nefazodone usually has no negative effects on libido or sexual functioning, and is actually sometimes used as an antidote to SSRI or SNRI induced impotence and anorgasmia in men.[8] More serious side effects include an allergic reaction, fainting, or painful/prolonged erection. Less serious reactions of nefazodone include dizziness, lightheadedness, fatigue, upset stomach, insomnia; dry mouth; constipation; or blurred/abnormal vision.[9]
[edit] Interactions
Nefazodone is a potent inhibitor of CYP3A4, an isozyme of the cytochrome P450 system, and may therefore interact adversely with many commonly-used medications that are metabolized by CYP3A4.[1][10]
[edit] Advantages
Nefazodone's claimed advantages over other antidepressants include reduced possibility of disturbed sleep or sexual dysfunction, and ability to treat some patients who did not respond to other antidepressant drugs.
Nefazodone, though an antidepressant, may also be beneficial in the prophylaxis of migraines due to its antagonistic effects on the 5-HT2A[11] and 5-HT2C receptors[12][13] It has a more favorable side effect profile than amitriptyline, a tricyclic antidepressant commonly used for migraine prophylaxis.
[edit] See also
[edit] References
- ^ a b Lexi-Comp (September 2008). "Nefazodone". The Merck Manual Professional. http://www.merck.com/mmpe/lexicomp/nefazodone.html. Retrieved on November 29, 2008.
- ^ Rxlist.com: "Nefazodone Prescribing Information", accessed 8 January 2007.]
- ^ FDA Orange Book, accessed 15 January 2006.
- ^ About.com: "Serzone Pulled from U.S. Market", accessed 15 January 2006.
- ^ a b c Cusack B, Nelson A, Richelson E. (1994). "Binding of Antidepressants to Human Brain Receptors: Focus on Newer Generation Compounds.". Psychopharmacology (Berl). 114 (4): 559-565. PMID 7855217.
- ^ Sanchez, C; J. Hyttel (1999). "Comparison of the Effects of Antidepressants and Their Metabolites on Reuptake of Biogenic Amines and on Receptor Binding". Celular and Molecular Neurobiology 19 (4): 467–89. doi:.
- ^ a b Tatsumi M, Groshan K, Blakely RD, Richelson E. (1997). "Pharmacological Profile of Antidepressants and Related Compounds at Human Monoamine Transporters.". Eur J Pharmacol. 340 (2-3): 249-258. PMID 9537821.
- ^ http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_684.html
- ^ http://www.drugs.com/serzone.html
- ^ Spina E, Santoro V, D'Arrigo C (July 2008). "Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update". Clin Ther 30 (7): 1206–27. doi:. PMID 18691982. http://linkinghub.elsevier.com/retrieve/pii/S0149-2918(08)80047-1.
- ^ Saper JR, Lake AE, Tepper SJ.(2001) "Nefazodone for chronic daily headache prophylaxis: an open-label study." Headache. 2001 May;41(5):465-74.PMID: 11380644
- ^ Mylecharane EJ.(1991)"5-HT2 receptor antagonists and migraine therapy."1: J Neurol. 1991;238 Suppl 1:S45-52.PMID: 2045831
- ^ Millan MJ.(2005)"Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies." 2005 Sep-Oct;60(5):441-60. PMID: 16433010
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Nefazodone".
