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药品详细

Sertraline(舍曲林)

化学结构式图
中文名
舍曲林
英文名
Sertraline
分子式
C17H17Cl2N
化学名
(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine
分子量
Average: 306.23
Monoisotopic: 305.073804963
CAS号
79617-96-2
ATC分类
N06A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Sertraline hydrochloride belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache (see Toxicity section below for a more detailed listing of side effects). Compared to other agents in this class, sertraline may cause greater diarrheal and male sexual dysfunction effects. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Sertraline may be used to treat major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (social phobia).

生产厂家
  • Actavis elizabeth llc
  • Actavis totowa llc
  • Apotex inc
  • Aurobindo pharma ltd
  • Austarpharma llc
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Hikma pharmaceuticals
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lupin ltd
  • Matrix laboratories ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Pfizer pharmaceuticals inc
  • Pliva hrvatska doo
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Watson laboratories inc
  • Wockhardt ltd
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Couzin J: The brains behind blockbusters. Science. 2005 Jul 29;309(5735):728. Pubmed
  2. Fabre LF, Abuzzahab FS, Amin M, Claghorn JL, Mendels J, Petrie WM, Dube S, Small JG: Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry. 1995 Nov 1;38(9):592-602. Pubmed
  3. Kronig MH, Apter J, Asnis G, Bystritsky A, Curtis G, Ferguson J, Landbloom R, Munjack D, Riesenberg R, Robinson D, Roy-Byrne P, Phillips K, Du Pont IJ: Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. J Clin Psychopharmacol. 1999 Apr;19(2):172-6. Pubmed
  4. Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, Farfel GM: Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2000 Apr 12;283(14):1837-44. Pubmed
  5. Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, Parry B, Pearlstein T, Severino S, Stout A, Stone A, Harrison W: Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA. 1997 Sep 24;278(12):983-8. Pubmed
  6. Shelton RC: The role of sertraline in the management of depression. Clin Ther. 1994 Sep-Oct;16(5):768-82; discussion 767. Pubmed
  7. Murdoch D, McTavish D: Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs. 1992 Oct;44(4):604-24. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Tametralines
Substructures
  • Naphthalenes
  • Tametralines
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aromatic compounds
  • Cyclohexenes and Derivatives
适应症
药理
Indication For the management of major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder with or without agoraphobia, premenstrual dysphoric disorder, social phobia, premature ejaculation, and vascular headaches.
Pharmacodynamics Sertraline, an antidepressant drug similar to citalopram, fluoxetine, and paroxetine, is of the selective serotonin reuptake inhibitor (SSRI) type. Sertraline has one active metabolite and, like the other SSRIs, have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not have clinically important anticholinergic, antihistamine, or adrenergic blocking activity.
Mechanism of action The exact mechanism of action sertraline is not fully known, but the drug appears to selectively inhibit the reuptake of serotonin at the presynaptic membrane. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. It is suggested that these modifications are responsible for the antidepressant action observed during long term administration of antidepressants. It has also been hypothesized that obsessive-compulsive disorder is caused by the dysregulation of serotonin, as it is treated by sertraline, and the drug corrects this imbalance.
Absorption The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects administered a single dose with and without food. For the tablet, AUC was slightly increased when drug was administered with food but the Cmax was 25% greater, while the time to reach peak plasma concentration (Tmax) decreased from 8 hours post-dosing to 5.5 hours. For the oral concentrate, Tmax was slightly prolonged from 5.9 hours to 7.0 hours with food.
Volume of distribution Not Available
Protein binding 98% bound to serum proteins, principally to albumin and α1-acid glycoprotein
Metabolism
Extensively metabolized in the liver. Sertraline metabolism involves N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes N-demethylation primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Deamination occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline N-carbamoyl glucuronidation has also been observed in human liver microsomes.

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

Substrate Enzymes Product
Sertraline
norsertraline Details
Route of elimination Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination.
Half life The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of desmethylsertraline is approximately 62-104 hours.
Clearance Not Available
Toxicity Symptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome. The most frequently observed side effects include: GI effects such as nausea, diarrhea or loose stools, dyspepsia, and dry mouth; nervous system effects such as somnolence, dizziness, insomnia, and tremor; sexual dysfunction in males (principally ejaculatory delay); and sweating.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 243-245 °C Not Available
water solubility 3.5mg/L Not Available
logP 5.1 Not Available
Predicted Properties
Property Value Source
water solubility 1.45e-04 g/l ALOGPS
logP 5.06 ALOGPS
logP 5.15 ChemAxon
logS -6.3 ALOGPS
pKa (strongest basic) 9.85 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 12.03 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 85.74 ChemAxon
polarizability 32.44 ChemAxon
药物相互作用
Drug Interaction
Almotriptan Increased risk of CNS adverse effects
Carbamazepine Sertraline increases the effect of carbamazepine
Carvedilol The SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, carvedilol.
Cilostazol Sertraline increases the effect of cilostazol
Clarithromycin Possible serotoninergic syndrome with this combination
Clozapine The antidepressant increases the effect of clozapine
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil Possible antagonism of action
Eletriptan Increased risk of CNS adverse effects
Erythromycin Possible serotoninergic syndrome with this combination
Fosphenytoin Sertraline increases the effect of hydantoin
Frovatriptan Increased risk of CNS adverse effects
Galantamine Possible antagonism of action
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Isocarboxazid Possible severe adverse reaction with this combination
Ketoprofen Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.
Linezolid Combination associated with possible serotoninergic syndrome
Metoprolol The SSRI increases the effect of the beta-blocker
Moclobemide Possible severe adverse reaction with this combination
Naratriptan Increased risk of CNS adverse effects
Oxycodone Increased risk of serotonin syndrome
Phenelzine Possible severe adverse reaction with this combination
Phenytoin Sertraline increases the effect of hydantoin
Pimozide The SSRI, sertraline, increases the effect and toxicity of pimozide.
Propafenone Fluoxetine increases the effect and toxicity of propafenone
Propranolol The SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, propranolol.
Rasagiline Possible severe adverse reaction with this combination
Tamoxifen Sertraline may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Sertraline, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Sertraline is initiated, discontinued, or dose changed.
Terbinafine Terbinafine may reduce the metabolism and clearance of Sertraline. Consider alternate therapy or monitor for therapeutic/adverse effects of Sertraline if Terbinafine is initiated, discontinued or dose changed.
Tiaprofenic acid Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
Tipranavir Tipranavir increases the concentration of Sertraline. The Sertraline dose may require an adjustment.
Tolmetin Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
Tolterodine Sertraline may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tramadol Tramadol increases the risk of serotonin syndrome and seizures. Sertraline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Sertraline may decrease the effect of Tramadol by decreasing active metabolite production.
Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Sertraline. Monitor for increased bleeding during concomitant thearpy.
Trimipramine The SSRI, Sertraline, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Sertraline is initiated, discontinued or dose changed.
Triprolidine The CNS depressants, Triprolidine and Sertraline, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and sertraline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
食物相互作用
  • Avoid alcohol.
  • Avoid St.John's Wort.
  • Avoid taking with grapefruit juice.
  • Take with food.

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