Tìm theo
Paroxetine
Các tên gọi khác (5 ) :
  • (-)-(3S,4R)-4-(P-Fluorophenyl)-3-((3,4-(methylenedioxy)phenoxy)methyl)piperidine
  • (3S-trans)-3-((1,3-Benzodioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine
  • Paroxetina
  • Paroxetine
  • Paroxetinum
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 61869-08-7
ATC: N06AB05
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C19H20FNO3
PTK: 329.3654
Paroxetine hydrochloride and paroxetine mesylate belong 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 complete listing of side effects). Side effects generally occur during the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Paroxetine hydrochloride and mesylate are considered therapeutic alternatives rather than generic equivalents by the US Food and Drug Administration (FDA); both agents contain the same active moiety (i.e. paroxetine), but are formulated as different salt forms. Clinical studies establishing the efficacy of paroxetine in various conditions were performed using paroxetine hydrochloride. Since both agents contain the same active moiety, the clinical efficacy of both agents is thought to be similar. Paroxetine may be used to treat major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive-compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) and premenstrual dysphoric disorder (PMDD). Paroxetine has the most evidence supporting its use for anxiety-related disorders of the SSRIs. It has the greatest anticholinergic activity of the agents in this class and compared to other SSRIs, paroxetine may cause greater weight gain, sexual dysfunction, sedation and constipation.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H20FNO3
Phân tử khối
329.3654
Monoisotopic mass
329.142721716
InChI
InChI=1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1
InChI Key
InChIKey=AHOUBRCZNHFOSL-YOEHRIQHSA-N
IUPAC Name
(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
Traditional IUPAC Name
paroxetine
SMILES
FC1=CC=C(C=C1)[C@@H]1CCNC[C@H]1COC1=CC2=C(OCO2)C=C1
Độ tan chảy
147-150 °C (mesylate salt)
Độ hòa tan
>1 g/mL (mesylate salt)
logP
3.6
logS
-4.6
pKa (Strongest Basic)
9.77
PSA
39.72 Å2
Refractivity
88.02 m3·mol-1
Polarizability
34.48 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Paroxetine, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, has no active metabolites and has the highest specificity for serotonin receptors of all the SSRIs. It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, social and general anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder, premature ejaculation, and hot flashes of menopause in women with breast cancer. In human platelets, paroxetine blocks the uptake of serotonin. It has weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic alpha1-, alpha2-, beta-adrenergic-, dopamine (D2)-, 5-HT1-, 5-HT2-, and histamine (H1)-receptors.
Cơ Chế Tác Dụng : Paroxetine hydrochloride and paroxetine mesylate belong 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 complete listing of side effects). Side effects generally occur during the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Paroxetine hydrochloride and mesylate are considered therapeutic alternatives rather than generic equivalents by the US Food and Drug Administration (FDA); both agents contain the same active moiety (i.e. paroxetine), but are formulated as different salt forms. Clinical studies establishing the efficacy of paroxetine in various conditions were performed using paroxetine hydrochloride. Since both agents contain the same active moiety, the clinical efficacy of both agents is thought to be similar. Paroxetine may be used to treat major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive-compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) and premenstrual dysphoric disorder (PMDD). Paroxetine has the most evidence supporting its use for anxiety-related disorders of the SSRIs. It has the greatest anticholinergic activity of the agents in this class and compared to other SSRIs, paroxetine may cause greater weight gain, sexual dysfunction, sedation and constipation. Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake. Paroxetine likely inhibits the reuptake of serotonin at the neuronal membrane, enhances serotonergic neurotransmission by reducing turnover of the neurotransmitter, therefore it prolongs its activity at synaptic receptor sites and potentiates 5-HT in the CNS; paroxetine is more potent than both sertraline and fluoxetine in its ability to inhibit 5-HT reuptake. Compared to the tricyclic antidepressants, SSRIs have dramatically decreased binding to histamine, acetylcholine, and norepinephrine receptors. The mechanism of action for the treatment of vasomotor symptoms is unknown.
Dược Động Học :
▧ Absorption :
Paroxetine hydrochloride is slowly, but completely absorbed following oral administration. Paroxetine mesylate salt is also completely absorbed after oral dosing. The oral bioavailability appears to be low due to extensive first-pass metabolism. Paroxetine hydrochloride oral tablets and suspension are reportedly bioequivalent. Absorption of either salt form is not substantially affected by food. Peak concentrations of Brisbelle (mesylate salt) were reached at 6 hours (3 to 8 hours range). Steady state Cmax was 13.10 ng/mL. The steady state AUC (0-last) was 237 hr*ng/mL. Paroxetine mesylate generally follows non-linear pharmacokinetics because CYP2D6, the enzyme that is part responisible for paroxetine metabolism, is readily saturable.
▧ Volume of Distribution :
3.1-28 L/kg observed in animal studies. Paroxetine distributes throughout the body, including the central nervous system, with only 1% remaining in the plasma.
▧ Protein binding :
~ 95% bound to plasma proteins.
▧ Metabolism :
Paroxetine is extensively metabolized after oral administration, likely in the liver. The main metabolites are polar and conjugated products of oxidation and methylation, which are readily eliminated by the body. The predominant metabolites are glucuronic acid and sulfate conjugates. Paroxetine metabolites do not possess significant pharmacologic activity (less than 2% that of parent compound). Paroxetine is metabolized by cytochrome P450 (CYP) 2D6. Enzyme saturation appears to account for the nonlinear pharmacokinetics observed with increasing dose and duration of therapy.
▧ Route of Elimination :
Approximately 64% of a 30 mg oral solution of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites. Approximately 36% of the dose was excreted in the feces (via bile), mostly as metabolites and less than 1% as parent compound.
▧ Half Life :
21-24 hours
Độc Tính : LD50=500mg/kg (orally in mice). Symptoms of overdose include: coma, dizziness, drowsiness, facial flushing, nausea, sweating, tremor, vomiting. Side effects include: nervous system effects such as asthenia, somnolence, dizziness, insomnia, tremor, and nervousness; GI effects such as nausea, decreased appetite, constipation, diarrhea, and dry mouth; impotence, ejaculatory dysfunction (principally ejaculatory delay), and other male genital disorders; female genital disorders (principally anorgasmia or difficulty reaching climax/orgasm); and sweating. Discontinuation syndrome may occur with abrupt withdrawal. Symptoms of discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory changes, and hyperactivity.
Chỉ Định : Labeled indications include: major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive-compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). Unlabeled indications include: eating disorders, impulse control disorders, vasomotor symptoms of menopause, obsessive-compulsive disorder (OCD) in children, and mild dementia-associated agitation in nonpsychotic individuals. Brisdelle, which consists of paroxetine mesylate is indicated for the treatment of moderate to severe vasomotor symptoms (like hot flashes) associated with menopause.
Tương Tác Thuốc :
  • Acenocoumarol The SSRI, paroxetine, increases the effect of the anticoagulant, acenocoumarol.
  • Almotriptan Increased risk of CNS adverse effects
  • Amphetamine Risk of serotoninergic syndrome
  • Anisindione The SSRI, paroxetine, increases the effect of the anticoagulant, anisindione.
  • Asenapine Paroxetine is a substrate of CYP2D6 and concomitant therapy with asenapine (CYP2D6 inhibitor) increases concentrations of paroxetine 2-fold. May require dosing adjustments.
  • Atomoxetine The CYP2D6 inhibitor, paroxetine, may increase the effect and toxicity of atomoxetine.
  • Benzphetamine Amphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor patients closely for signs and symptoms of serotonin syndrome (e.g., agitation, tremor, tachycardia, etc.) when using amphetamines and serotonin modulators in combination.
  • Carvedilol The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dexfenfluramine Risk of serotoninergic syndrome
  • Dextroamphetamine Risk of serotoninergic syndrome
  • Dextromethorphan Combination associated with possible serotoninergic syndrome
  • Dicoumarol The SSRI, paroxetine, increases the effect of anticoagulant, dicumarol.
  • Diethylpropion Risk of serotoninergic syndrome
  • Dihydrocodeine Opioid analgesics may enhance the 5HT effects of SSRIs to cause serotonin syndrome. It is recommended to monitor therapy.
  • Eletriptan Increased risk of CNS adverse effects
  • Fenfluramine Risk of serotoninergic syndrome
  • Frovatriptan Increased risk of CNS adverse effects
  • Galantamine Paroxetine increases the effect and toxicity of galantamine
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
  • Iloperidone Paroxetine is a strong CYP2D6 inhibitor that increases serum concentration of iloperidone and likelihood of observing adverse effects such as QT prolongation. Reduce dose of iloperidone by 50%
  • 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
  • Mazindol Risk of serotoninergic syndrome
  • Mesoridazine Increased risk of cardiotoxicity and arrhythmias
  • Methamphetamine Risk of 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
  • Phendimetrazine Risk of serotoninergic syndrome
  • Phenelzine Possible severe adverse reaction with this combination
  • Phentermine Risk of serotoninergic syndrome
  • Phenylpropanolamine Risk of serotoninergic syndrome
  • Pimozide Increased risk of cardiotoxicity and arrhythmias.
  • Propafenone Paroxetine may increase the effect and toxicity of propafenone.
  • Propranolol The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
  • Rasagiline Possible severe adverse reaction with this combination
  • Risperidone The SSRI, paroxetine, increases the effect and toxicity of risperidone.
  • 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, paroxetine.
  • Sumatriptan Increased risk of CNS adverse effects
  • Tamoxifen Paroxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
  • Tamsulosin Paroxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Paroxetine is initiated, discontinued, or dose changed.
  • Terbinafine Terbinafine may reduce the metabolism and clearance of Paroxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Paroxetine if Terbinafine is initiated, discontinued or dose changed.
  • Tetrabenazine Paroxetine is a strong CYP2D6 inhibitor thus increasing half life of dihydrotetrabenazine moieties. Dose of tetrabenazine should be reduced
  • Thioridazine Increased risk of cardiotoxicity and arrhythmias
  • Tiaprofenic acid Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
  • Tipranavir Tipranavir increases the concentration of Paroxetine. The Paroxetine 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 Paroxetine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
  • Tramadol Tramadol may increase the risk of serotonin syndrome and seizures. Paroxetine 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, Paroxetine. Monitor for increased bleeding during concomitant thearpy.
  • Trimipramine The SSRI, Paroxetine, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Paroxetine is initiated, discontinued or dose changed.
  • Triprolidine The CNS depressants, Triprolidine and Paroxetine, 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.
  • Warfarin The SSRI, paroxetine, increases the effect of the anticoagulant, warfarin.
  • Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and paroxetine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
  • Zuclopenthixol Paroxetine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if paroxetine is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Capsule - Oral - 7.5 mg
Suspension - Oral - 10 mg/5 mL
Tablet - Oral - 10 mg, 20 mg, 30 mg, 40 mg
Tablet, extended release - Oral - 12.5 mg, 25 mg, 37.5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Aropax
  • Sản phẩm biệt dược : Brisdelle
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Paxil
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Paxil CR
  • Công ty :
    Sản phẩm biệt dược : PAXILCR
  • Công ty :
    Sản phẩm biệt dược : Pexeva
  • Công ty :
    Sản phẩm biệt dược : Sereupin
  • Công ty :
    Sản phẩm biệt dược : Seroxat
  • Công ty :
    Sản phẩm biệt dược : Seroxat CR
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00715
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=43815
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504821
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07415
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02362
ChemSpider
http://www.chemspider.com/Chemical-Structure.39888.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22416
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0029-3210-13
PharmGKB
http://www.pharmgkb.org/drug/PA450801
Wikipedia
http://en.wikipedia.org/wiki/Paroxetine
RxList
http://www.rxlist.com/cgi/generic/parox.htm
Drugs.com
http://www.drugs.com/paroxetine.html
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