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Identification
Name Paroxetine
Accession Number DB00715
Type small molecule
Groups approved
Description

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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Paroxetina [INN-Spanish]
Paroxetine Hcl
Paroxetinum [INN-Latin]
Salts Not Available
Brand names
Name Company
Aropax
Paxil GlaxoSmithKline
Paxil CR GlaxoSmithKline
Seroxat
Seroxat CR
Brand mixtures Not Available
Categories
  • Antidepressants
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin Uptake Inhibitors
  • Antidepressive Agents, Second-Generation
CAS number 61869-08-7
Weight Average: 329.3654
Monoisotopic: 329.142721716
Chemical Formula C19H20FNO3
InChI Key InChIKey=AHOUBRCZNHFOSL-YOEHRIQHSA-N
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
Plain Text
IUPAC Name
(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
SMILES
FC1=CC=C(C=C1)[C@@H]1CCNC[C@H]1COC1=CC2=C(OCO2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
Substructures
  • Acetals and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Dioxoles
  • Hydroquinones
  • Catechols
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Phenylpropylamines
  • Aryl Halides
  • Phenyl Esters
  • Piperidines
Pharmacology
Indication 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.
Pharmacodynamics 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.
Mechanism of action 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.
Absorption Paroxetine hydrochloride is slowly, but completely absorbed following oral administration. The oral bioavailability appears to be low due to extensive first-pass metabolism. Paroxetine hydrochloride oral tablets and suspension are reportedly bioequivalent. Paroxetine mesylate is completely following oral administration. Absorption of either salt form is not substantially affected by food.
Volume of distribution

3.1-28 L/kg observed in animal studies
Protein binding ~ 95% bound to plasma proteins.
Metabolism Paroxetine is extensively metabolized, 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 Paroxetine is extensively metabolized and the metabolites are primarily excreted in the urine and to some extent in the feces.
Half life 21-24 hours
Clearance Not Available
Toxicity 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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Apotex inc
  • Mylan pharmaceuticals inc
  • Actavis elizabeth llc
  • Alphapharm pty ltd
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Zydus pharmaceuticals usa inc
  • Noven therapeutics llc
Packagers
Dosage forms
Form Route Strength
Suspension Oral 10 mg/5 ml
Tablet, film coated Oral 10 mg
Tablet, film coated Oral 20 mg
Tablet, film coated Oral 30 mg
Tablet, film coated Oral 40 mg
Tablet, film coated, extended release Oral 12.5 mg
Tablet, film coated, extended release Oral 25 mg
Tablet, film coated, extended release Oral 37.5 mg
Prices
Unit description Cost Unit
Paxil 30 40 mg tablet Bottle 138.39 USD bottle
Paxil 30 30 mg tablet Bottle 131.0 USD bottle
Paxil 30 10 mg tablet Bottle 121.87 USD bottle
Pexeva 40 mg tablet 6.29 USD tablet
Pexeva 30 mg tablet 6.11 USD tablet
Pexeva 20 mg tablet 5.84 USD tablet
Pexeva 10 mg tablet 5.6 USD tablet
Paxil CR 37.5 mg 24 Hour tablet 4.5 USD tablet
Paxil 40 mg tablet 4.44 USD tablet
Paxil CR 25 mg 24 Hour tablet 4.37 USD tablet
Paxil cr 37.5 mg tablet 4.32 USD tablet
Paxil 30 mg tablet 4.2 USD tablet
Paxil cr 25 mg tablet 4.2 USD tablet
Paxil CR 12.5 mg 24 Hour tablet 4.18 USD tablet
Paxil 20 mg tablet 4.16 USD tablet
PARoxetine HCl 37.5 mg 24 Hour tablet 4.04 USD tablet
Paxil cr 12.5 mg tablet 4.02 USD tablet
PARoxetine HCl 25 mg 24 Hour tablet 3.93 USD tablet
Paxil 10 mg tablet 3.91 USD tablet
PARoxetine HCl 12.5 mg 24 Hour tablet 3.76 USD tablet
Paroxetine hcl 40 mg tablet 2.93 USD tablet
Paroxetine hcl 30 mg tablet 2.78 USD tablet
Paroxetine hcl 20 mg tablet 2.7 USD tablet
Paroxetine hcl 10 mg tablet 2.58 USD tablet
Paxil 30 mg Tablet 2.16 USD tablet
Pms-Paroxetine 40 mg Tablet 2.1 USD tablet
Paxil 20 mg Tablet 2.03 USD tablet
Apo-Paroxetine 30 mg Tablet 1.12 USD tablet
Co Paroxetine 30 mg Tablet 1.12 USD tablet
Mylan-Paroxetine 30 mg Tablet 1.12 USD tablet
Novo-Paroxetine 30 mg Tablet 1.12 USD tablet
Phl-Paroxetine 30 mg Tablet 1.12 USD tablet
Pms-Paroxetine 30 mg Tablet 1.12 USD tablet
Ratio-Paroxetine 30 mg Tablet 1.12 USD tablet
Sandoz Paroxetine 30 mg Tablet 1.12 USD tablet
Apo-Paroxetine 20 mg Tablet 1.05 USD tablet
Co Paroxetine 20 mg Tablet 1.05 USD tablet
Mylan-Paroxetine 20 mg Tablet 1.05 USD tablet
Novo-Paroxetine 20 mg Tablet 1.05 USD tablet
Phl-Paroxetine 20 mg Tablet 1.05 USD tablet
Pms-Paroxetine 20 mg Tablet 1.05 USD tablet
Ratio-Paroxetine 20 mg Tablet 1.05 USD tablet
Sandoz Paroxetine 20 mg Tablet 1.05 USD tablet
Paxil 10 mg/5ml Suspension 0.85 USD ml
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Patents
Country Patent Number Approved Expires (estimated)
United States 6703408 2002-10-21 2022-10-21
United States 5789449 1992-07-06 2009-07-06
Canada 2445678 2009-11-24 2016-07-19
Canada 2168829 1997-12-16 2016-02-05
Properties
State solid
Experimental Properties
Property Value Source
melting point 129-131 °C Not Available
logP 3.6 Not Available
Predicted Properties
Property Value Source
water solubility 8.53e-03 g/l ALOGPS
logP 3.1 ALOGPS
logP 3.15 ChemAxon
logS -4.6 ALOGPS
pKa (strongest basic) 9.77 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 39.72 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 88.02 ChemAxon
polarizability 34.48 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU: Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005 Nov;19(6):567-96. Pubmed
  2. Baldwin D, Bobes J, Stein DJ, Scharwachter I, Faure M: Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group. Br J Psychiatry. 1999 Aug;175:120-6. Pubmed
  3. Yonkers KA, Gullion C, Williams A, Novak K, Rush AJ: Paroxetine as a treatment for premenstrual dysphoric disorder. J Clin Psychopharmacol. 1996 Feb;16(1):3-8. Pubmed
  4. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B: Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol. 1998 Aug;18(4):274-81. Pubmed
  5. Waldinger MD, Zwinderman AH, Olivier B: SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram. J Clin Psychopharmacol. 2001 Dec;21(6):556-60. Pubmed
External Links
Resource Link
KEGG Drug D02362 Link_out
KEGG Compound C07415 Link_out
PubChem Compound 43815 Link_out
PubChem Substance 46504821 Link_out
ChemSpider 39888 Link_out
BindingDB 22416 Link_out
ChEBI 7936 Link_out
ChEMBL 7936 Link_out
Therapeutic Targets Database DAP001428 Link_out
PharmGKB PA450801 Link_out
Drug Product Database 2262746 Link_out
RxList http://www.rxlist.com/cgi/generic/parox.htm Link_out
Drugs.com http://www.drugs.com/paroxetine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Paroxetine Link_out
ATC Codes
  • N06AB05
AHFS Codes
  • 28:16.04.20
PDB Entries Not Available
FDA label show (299 KB)
MSDS show (51.2 KB)
Interactions
Drug Interactions
Drug Interaction
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
Dicumarol The SSRI, paroxetine, increases the effect of anticoagulant, dicumarol.
Diethylpropion Risk of serotoninergic syndrome
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.
Food Interactions
  • Take without regard to meals. Avoid alcohol.
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Scholze P, Zwach J, Kattinger A, Pifl C, Singer EA, Sitte HH: Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter. J Pharmacol Exp Ther. 2000 Jun;293(3):870-8. Pubmed
  2. Preuss UW, Soyka M, Bahlmann M, Wenzel K, Behrens S, de Jonge S, Kruger M, Bondy B: Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity. Psychiatry Res. 2000 Sep 25;96(1):51-61. Pubmed
  3. Haughey HM, Fleckenstein AE, Metzger RR, Hanson GR: The effects of methamphetamine on serotonin transporter activity: role of dopamine and hyperthermia. J Neurochem. 2000 Oct;75(4):1608-17. Pubmed
  4. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF, Kupfer DJ: Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology. 2000 Nov;23(5):587-90. Pubmed
  5. Wihlback AC, Sundstrom-Poromaa I, Allard P, Mjorndal T, Spigset O, Backstrom T: Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and serotonin 2A receptor binding. Obstet Gynecol. 2001 Sep;98(3):450-7. Pubmed
  6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

2. Sodium-dependent noradrenaline transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rubin RT: Paroxetine binding to the rat norepinephrine transporter in vivo. Biol Psychiatry. 2000 Nov 1;48(9):954-6. Pubmed
  2. Gilmor ML, Owens MJ, Nemeroff CB: Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002 Oct;159(10):1702-10. Pubmed
  3. Nemeroff CB, Owens MJ: Neuropharmacology of paroxetine. Psychopharmacol Bull. 2003 Spring;37 Suppl 1:8-18. Pubmed
  4. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

3. 5-hydroxytryptamine 2A receptor

Pharmacological action: unknown
Actions: other/unknown

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bixo M, Allard P, Backstrom T, Mjorndal T, Nyberg S, Spigset O, Sundstrom-Poromaa I: Binding of [3H]paroxetine to serotonin uptake sites and of [3H]lysergic acid diethylamide to 5-HT2A receptors in platelets from women with premenstrual dysphoric disorder during gonadotropin releasing hormone treatment. Psychoneuroendocrinology. 2001 Aug;26(6):551-64. Pubmed
  2. Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH: The effect of paroxetine on 5-HT receptors in depression: an [(18)F]setoperone PET imaging study. Am J Psychiatry. 2001 Jan;158(1):78-85. Pubmed

4. Muscarinic acetylcholine receptor M1

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

5. Muscarinic acetylcholine receptor M2

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

6. Muscarinic acetylcholine receptor M3

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P20309 Link_out
Gene: CHRM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

7. Muscarinic acetylcholine receptor M4

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase

Organism class: human
UniProt ID: P08173 Link_out
Gene: CHRM4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

8. Muscarinic acetylcholine receptor M5

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P08912 Link_out
Gene: CHRM5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
  2. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. Pubmed
  3. Ozdemir V, Naranjo CA, Herrmann N, Reed K, Sellers EM, Kalow W: Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo. Clin Pharmacol Ther. 1997 Sep;62(3):334-47. Pubmed
  4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2B6

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19