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药品详细

Citalopram(西酞普兰)

化学结构式图
中文名
西酞普兰
英文名
Citalopram
分子式
C20H21FN2O
化学名
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile
分子量
Average: 324.3919
Monoisotopic: 324.163791509
CAS号
59729-33-8
ATC分类
N06A 未知;N06A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Citalopram hydrobromide belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Citalopram and its N-demethylated metabolites exist as a racemic mixture but its effects are largely due to the S-enantiomer, S-citalopram and S-demthylcitalopram. 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. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Citalopram is approved for treatment of depression. Unlabeled indications include mild dementia-associated agitation in nonpsychotic patients, smoking cessation, ethanol abuse, obsessive-compulsive disorder (OCD) in children, and diabetic neuropathy. Citalopram has the fewest drug-drug interactions of the SSRIs.

生产厂家
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Amneal pharmaceuticals ny llc
  • Apotex inc etobicoke site
  • Apotex inc richmond hill
  • Aurobindo pharma ltd
  • Aurobindo pharma ltd inc
  • Biovail laboratories international srl
  • Caraco pharmaceutical laboratories ltd
  • Corepharma llc
  • Dr reddys laboratories ltd
  • Epic pharma llc
  • Forest laboratories inc
  • Glenmark generics ltd
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Matrix laboratories inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Natco pharma ltd
  • Pliva inc
  • Roxane laboratories inc
  • Sandoz inc
  • Silarx pharmaceuticals inc
  • Taro pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Torrent pharmaceuticals ltd
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Sindrup SH, Bjerre U, Dejgaard A, Brosen K, Aaes-Jorgensen T, Gram LF: The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Clin Pharmacol Ther. 1992 Nov;52(5):547-52. Pubmed
  2. Atmaca M, Kuloglu M, Tezcan E, Semercioz A: The efficacy of citalopram in the treatment of premature ejaculation: a placebo-controlled study. Int J Impot Res. 2002 Dec;14(6):502-5. Pubmed
  3. Andersen G, Vestergaard K, Riis JO: Citalopram for post-stroke pathological crying. Lancet. 1993 Oct 2;342(8875):837-9. Pubmed
  4. Clayton A, Keller A, McGarvey EL: Burden of phase-specific sexual dysfunction with SSRIs. J Affect Disord. 2006 Mar;91(1):27-32. Epub 2006 Jan 20. Pubmed
  5. Baumann P: Pharmacology and pharmacokinetics of citalopram and other SSRIs. Int Clin Psychopharmacol. 1996 Mar;11 Suppl 1:5-11. Pubmed
  6. FDA label
  7. Hyttel J, Bogeso KP, Perregaard J, Sanchez C: The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect. 1992;88(2):157-60. Pubmed
  8. Caccia S: Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet. 1998 Apr;34(4):281-302. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzofurans
  • Benzyl Alcohols and Derivatives
  • Nitriles and Derivatives
Substructures
  • Benzofurans
  • Benzyl Alcohols and Derivatives
  • Nitriles and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cyanides
  • Aliphatic and Aryl Amines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Aryl Halides
适应症
药理
Indication For the treatment of depression. Unlabeled indications include: treatment of mild dementia-associated agitation in nonpsychotic patients, smoking cessation, ethanol abuse, obsessive-compulsive disorder (OCD) in children, and diabetic neuropathy.
Pharmacodynamics Citalopram is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that citalopram is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Citalopram has no significant affinity for adrenergic (α1, α2, β), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of citalopram was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase.
Mechanism of action The antidepressant, antiobsessive-compulsive, and antibulimic actions of citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Citalopram blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
Absorption Rapidly and well absorbed from the GI tract. Peak plasma concentrations occur within 4 hours of a single orally administered dose. Bioavailability is 80% following oral administration. Food does not affect absorption.
Volume of distribution
  • 12 L/kg
    Citalopram is highly lipophilic and likely widely distributed throughout the body, including the blood-brain-barrier. However, its metabolite, demethylcitalopram does not cross the barrier well.
Protein binding Citalopram, dimethylcitalopram, and didemethylcitalopram is 80% bound to plasma proteins.
Metabolism
Citalopram is metabolized mainly in the liver via N-demethylation to its principle metabolite, demethylcitalopram. Other metabolites include didemethylcitalopram, citalopram N-oxide, and a deaminated propionic acid derivative. However, the predominant entity in plasma is unchanged citalopram. Cytochrome P450 (CYP) 3A4 and 2C19 isozymes appear to be principally involved in producing demethylcitalopram. Demethylcitalopram appears to be further N-demethylated by CYP2D6 to didemethylcitalopram. Citalopram metabolites possess little pharmacologic activity in comparison to their parent compound and do not likely contribute to the clinical effect of the drug.

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

Substrate Enzymes Product
Citalopram
Citalopram N-oxide Details
Citalopram
N-Desmethylcitalopram Details
Citalopram
    		Citalopram propionic acid Details
    Citalopram
      		Didemethylcitalopram Details
      Citalopram
        		Desmethylcitalopram Details
        Route of elimination 12-23% of an oral dose of citalopram is recovered unchanged in the urine, while 10% of the dose is recovered in the feces.
        Half life 35 hours
        Clearance

        The systemic clearance of citalopram was 330 mL/min, with approximately 20% of that due to renal clearance.
        Toxicity Symptoms most often accompanying citalopram overdose, alone or in combination with other drugs and/or alcohol, included dizziness, sweating, nausea, vomiting, tremor, somnolence, and sinus tachycardia. In more rare cases, observed symptoms included amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, rhabdomyolysis, and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose. Withdrawal symptoms include flu-like symptoms, insomnia, nausea, imbalance, sensory changes and hyperactivity.
        Affected organisms
        • Humans and other mammals
        Pathways
        Pathway Name SMPDB ID
        Smp00424 Citalopram Pathway SMP00424
        理化性质
        Properties
        State solid
        Experimental Properties
        Property Value Source
        melting point 182-183 °C Not Available
        water solubility Sparingly soluble FDA label
        logP 3.5 Not Available
        Predicted Properties
        Property Value Source
        water solubility 5.88e-03 g/l ALOGPS
        logP 3.58 ALOGPS
        logP 3.76 ChemAxon
        logS -4.7 ALOGPS
        pKa (strongest basic) 9.78 ChemAxon
        physiological charge 1 ChemAxon
        hydrogen acceptor count 3 ChemAxon
        hydrogen donor count 0 ChemAxon
        polar surface area 36.26 ChemAxon
        rotatable bond count 5 ChemAxon
        refractivity 94.02 ChemAxon
        polarizability 35.4 ChemAxon
        药物相互作用
        Drug Interaction
        Acenocoumarol The SSRI, citalopram, increases the effect of anticoagulant, acenocoumarol.
        Almotriptan Increased risk of CNS adverse effects
        Anisindione The SSRI, citalopram, increases the effect of anticoagulant, anisindione.
        Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
        Carvedilol The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
        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.
        Dicumarol The SSRI, citalopram, increases the effect of anticoagulant, dicumarol.
        Eletriptan Increased risk of CNS adverse effects
        Erythromycin Possible serotoninergic syndrome with this combination
        Etravirine Citalopram, when used concomitantly with etravirine (a CYP2C19 inhibitor), may experience an increase in serum concentration. It is recommended to maintain the dose of citalopram below 20mg/day, and to monitor for toxicity. The symptoms which often accompany citalopram overdose are dizziness, sweating, nausea, vomiting, tremor, somnolence,sinus tachycardia,amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, rhabdomyolysis, acute renal failure, and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and torsade de pointes).
        Frovatriptan Increased risk of CNS adverse effects
        Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
        Isocarboxazid Possible severe adverse reaction with this combination
        Josamycin Possible serotoninergic sydrome 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
        Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
        Metoprolol The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.
        Moclobemide Possible serotoninergic syndrome
        Naratriptan Increased risk of CNS adverse effects
        Oxycodone Increased risk of serotonin syndrome
        Phenelzine Possible severe adverse reaction with this combination
        Pimozide The SSRI, citalopram, may increase the effect and toxicity of pimozide.
        Propranolol The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, propranolol.
        Rasagiline Possible severe adverse reaction with this combination
        Rizatriptan Increased risk of CNS adverse effects
        Selegiline Possible severe adverse reaction with this combination
        Sibutramine Risk of serotoninergic syndrome
        St. John's Wort St. John's Wort increases the effect and toxicity of the SSRI, citalopram.
        Sumatriptan Increased risk of CNS adverse effects
        Telithromycin Telithromycin may reduce clearance of Citalopram. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Citalopram if Telithromycin is initiated, discontinued or dose changed.
        Tiaprofenic acid Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
        Ticlopidine Ticlopidine may decrease the metabolism and clearance of Citalopram. Consider alternate therapy or monitor for adverse/toxic effects of Citalopram if Ticlopidine is initiated, discontinued or dose changed.
        Tolmetin Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
        Tramadol The use of two serotonin modulators, such as citalopram and tramadol, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
        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, Citalopram. Monitor for increased bleeding during concomitant thearpy.
        Trimipramine The SSRI, Citalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Citalopram is initiated, discontinued or dose changed.
        Triprolidine The CNS depressants, Triprolidine and Citalopram, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
        Troleandomycin Possible serotoninergic syndrome with this combination
        Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
        Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of citalopram by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of citalopram if voriconazole is initiated, discontinued or dose changed.
        Warfarin The SSRI, citalopram, increases the effect of anticoagulant, warfarin.
        Ziprasidone Additive QTc-prolongation may occur increasing the risk of life-threatening ventricular arrhythmias and torsade de pointes. Concomitant therapy should be avoided.
        Zolmitriptan The use of two serotonin modulators, such as zolmitriptan and citalopram, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
        Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
        食物相互作用
        • Avoid alcohol.
        • Avoid St.John's Wort.
        • Take without regard to meals.

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