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药品详细

Nefazodone(奈法唑酮)

化学结构式图
中文名
奈法唑酮
英文名
Nefazodone
分子式
C25H32ClN5O2
化学名
1-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-3-ethyl-4-(2-phenoxyethyl)-4,5-dihydro-1H-1,2,4-triazol-5-one
分子量
Average: 470.007
Monoisotopic: 469.224453
CAS号
83366-66-9
ATC分类
N06A 未知
药物类型
small molecule
阶段
approved, withdrawn
商品名
同义名
基本介绍

Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States. [Wikipedia]

生产厂家
  • Bristol myers squibb co pharmaceutical research institute
  • Dr reddys laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenols and Derivatives
  • Ethers
  • Halobenzenes
  • Anisoles
  • Phenyl Esters
  • Anilines
Substructures
  • Triazoles
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Imines
  • Cyanamides
  • Phenyl Esters
  • Anilines
适应症
药理
Indication For the treatment of depression.
Pharmacodynamics Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.
Mechanism of action Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.
Absorption Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%).
Volume of distribution
  • 0.22 to 0.87 L/kg
Protein binding Greater than 99% (in vitro, human plasma proteins).
Metabolism
Hepatic.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Nefazodone
hydroxynefazodone Details
Route of elimination Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine.
Half life 2-4 hours
Clearance Not Available
Toxicity Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 83.5 °C PhysProp
logP 4.7 Not Available
Predicted Properties
Property Value Source
water solubility 6.98e-02 g/l ALOGPS
logP 3.71 ALOGPS
logP 4.65 ChemAxon
logS -3.8 ALOGPS
pKa (strongest basic) 7.09 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 51.62 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 132.38 ChemAxon
polarizability 51.85 ChemAxon
药物相互作用
Drug Interaction
Abiraterone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
Almotriptan Increased risk of CNS adverse effects
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nefazodone is initiated, discontinued or dose changed.
Bromazepam Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if nefazodone is initiated, discontinued or dose changed. Dosage adjustments may be required.
Buspirone Nefazodone increases the effect of buspirone
Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
Carbamazepine Nefazodone increases the effect of carbamazepine
Cerivastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if nefazodone is initiated, discontinued or dose changed.
Cilostazol Nefazodone increases the effect of cilostazol
Cisapride Nefazodone increases serum levels of cisapride
Cyclosporine The antidepressant increases the effect and toxicity of cyclosporine
Dabigatran etexilate P-Glycoprotein inducers such as nefazodone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
Dabrafenib Strong CYP3A4 inhibitors may increase levels of dabrafenib. Consider alternate therapy.
Dantrolene Nefazodone may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nefazodone is initiated, discontinued or dose changed.
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroergotamine Possible ergotism and severe ischemia with this combination
Dronedarone Nefazodone is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
Eletriptan Increased risk of CNS adverse effects
Eplerenone Nefazodone increases the effect and toxicity of eplerenone
Ergotamine Possible ergotism and severe ischemia with this combination
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Frovatriptan Increased risk of CNS adverse effects
Isocarboxazid Possible severe adverse reaction with this combination
Linezolid Combination associated with possible serotoninergic syndrome
Loratadine Increased risk of cardiotoxicity
Lovastatin Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if nefazodone is initiated, discontinued or dose changed.
Naratriptan Increased risk of CNS adverse effects
Pazopanib Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
Phenelzine Possible severe adverse reaction with this combination
Pimozide Nefazodone may increase the effect and toxicity of pimozide.
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Rasagiline Possible severe adverse reaction with this combination
Rizatriptan Increased risk of CNS adverse effects
Saxagliptin Nefazodone is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
Sibutramine Risk of serotoninergic syndrome
Simvastatin Nefazodone may increase the effect and toxicity of simvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nefazodone is initiated, discontinued or dose changed.
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
St. John's Wort St. John's Wort increases the effect and toxicity of the SSRI, nefazodone.
Sumatriptan Increased risk of CNS adverse effects
Sunitinib Possible increase in sunitinib levels
Tacrolimus Nefazodone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nefazodone therapy is initiated, discontinued or altered.
Tadalafil Nefazodone may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Nefazodone may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Tamsulosin Nefazodone, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nefazodone is initiated, discontinued, or dose changed.
Telithromycin Co-administration may result in altered plasma concentrations of Nefazodone and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
Temsirolimus Nefazodone may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nefazodone is initiated, discontinued or dose changed.
Terbinafine Terbinafine may reduce the metabolism and clearance of Nefazodone. Consider alternate therapy or monitor for therapeutic/adverse effects of Nefazodone if Terbinafine is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tiagabine The strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nefazodone is initiated, discontinued or dose changed.
Tolterodine Nefazodone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Nefazodone is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
Tramadol Nefazodone may increase tramadol toxicity by decreasing tramadol metabolism and clearance. Increased risk of serotonin syndrome. Monitor for tramadol toxicity and symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. The CYP3A4 inhibitor, Nefazodone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for symtpoms of sertonin syndrome and changes in Trazodone efficacy/toxicity if Nefazodone is initiated, discontinued or dose changed.
Triazolam Nefazodone increases the effect of triazolam
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Nefazodone, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nefazodone is initiated, discontinued or dose changed.
Triprolidine The CNS depressants, Triprolidine and Nefazodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Vardenafil Nefazodone, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Vemurafenib Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Verapamil Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nefazodone is initiated, discontinued or dose changed.
Vinblastine Nefazodone, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nefazodone is initiated, discontinued or dose changed.
Vincristine Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nefazodone is initiated, discontinued or dose changed.
Vinorelbine Nafazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nefazodone is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nefazodone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nefazodone if voriconazole is initiated, discontinued or dose changed.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and nafazodone, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Zolpidem Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if nefazodone is initiated, discontinued or dose changed.
Zonisamide Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nefazodone is initiated, discontinued or dose changed.
Zopiclone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nefazodone is initiated, discontinued or dose changed.
食物相互作用
  • Avoid alcohol.
  • Avoid avocado.
  • Limit garlic, ginger, gingko, and horse chestnut.
  • Take this medication either consistently with or without food as instructed by your doctor.

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