QuickView for paroxetine (compound)

Summary
General Info

PubChem

PubChem Compound 10066032

Name:	Paroxetine
PubChem Compound ID:	10066032
Description:	A serotonin uptake inhibitor that is effective in the treatment of depression.
Molecular formula:	C₂₀H₂₂FNO₃
Molecular weight:	343.392 g/mol

DrugBank

Identification

Name:	Paroxetine
Name (isomeric):	DB00715
Drug Type:	small molecule
Description:	A serotonin uptake inhibitor that is effective in the treatment of depression.
Synonyms:	Paroxetina [INN-Spanish]; Paroxetinum [INN-Latin]; Paroxetine Hcl
Brand:	Pexeva, Paxil, Aropax, Seroxat, Seroxat CR, Paxil CR
Category:	Antidepressants, Antidepressive Agents, Second-Generation, Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Uptake Inhibitors
CAS number:	61869-08-7

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.
Pharmacology:	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, o... show more » 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. show less «
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; paro... show more » 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. show less «
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.
Protein binding:	~ 95% bound to plasma proteins.
Biotransformation:	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
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

Interactions

Food interaction:

Take without regard to meals. Avoid alcohol.

Drug interaction:

Phenelzine	Possible severe adverse reaction with this combination
Almotriptan	Increased risk of CNS adverse effects
Propranolol	The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
Dextromethorphan	Combination associated with possible serotoninergic syndrome
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.

Phenelzine	Possible severe adverse reaction with this combination
Almotriptan	Increased risk of CNS adverse effects
Propranolol	The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
Dextromethorphan	Combination associated with possible serotoninergic syndrome
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.
Phentermine	Risk of serotoninergic syndrome
Triprolidine	The CNS depressants, Triprolidine and Paroxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Isocarboxazid	Possible severe adverse reaction with this combination
Fenfluramine	Risk of serotoninergic syndrome
Dextroamphetamine	Risk of serotoninergic syndrome
Tiaprofenic acid	Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
Rasagiline	Possible severe adverse reaction with this combination
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Naratriptan	Increased risk of CNS adverse effects
Acenocoumarol	The SSRI, paroxetine, increases the effect of the anticoagulant, acenocoumarol.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Moclobemide	Possible severe adverse reaction with this combination
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.
Eletriptan	Increased risk of CNS adverse effects
St. John's Wort	St. John's Wort increases the effect and toxicity of the SSRI, paroxetine.
Propafenone	Paroxetine may increase the effect and toxicity of propafenone.
Ginkgo biloba	Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Rizatriptan	Increased risk of CNS adverse effects
Dexfenfluramine	Risk of serotoninergic syndrome
Methamphetamine	Risk of serotoninergic syndrome
Tramadol	Tramadol may increase the risk of serotonin syndrome and seizures. Paroxetine may decrease the effect of Tramadol by decreasing active metabolite production.
Mazindol	Risk of serotoninergic syndrome
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.
Selegiline	Possible severe adverse reaction with this combination
Galantamine	Paroxetine increases the effect and toxicity of galantamine
Linezolid	Combination associated with possible serotoninergic syndrome
Warfarin	The SSRI, paroxetine, increases the effect of the anticoagulant, warfarin.
Diethylpropion	Risk of serotoninergic syndrome
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Pimozide	Increased risk of cardiotoxicity and arrhythmias.
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.
Amphetamine	Risk of serotoninergic syndrome
Dicumarol	The SSRI, paroxetine, increases the effect of anticoagulant, dicumarol.
Carvedilol	The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
Phenylpropanolamine	Risk of serotoninergic syndrome
Anisindione	The SSRI, paroxetine, increases the effect of the anticoagulant, anisindione.
Tolmetin	Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Atomoxetine	The CYP2D6 inhibitor, paroxetine, may increase the effect and toxicity of atomoxetine.
Oxycodone	Increased risk of serotonin syndrome
Frovatriptan	Increased risk of CNS adverse effects
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.
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.
Tipranavir	Tipranavir increases the concentration of Paroxetine. The Paroxetine dose may require an adjustment.
Sibutramine	Risk of serotoninergic syndrome
Sumatriptan	Increased risk of CNS adverse effects
Treprostinil	The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Paroxetine. Monitor for increased bleeding during concomitant thearpy.
Metoprolol	The SSRI increases the effect of the beta-blocker
Phendimetrazine	Risk of serotoninergic syndrome
Ketoprofen	Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.
Tolterodine	Paroxetine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
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.
Risperidone	The SSRI, paroxetine, increases the effect and toxicity of risperidone.

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Targets

Sodium-dependent serotonin transporter

Sodium-dependent noradrenaline transporter

5-hydroxytryptamine 2A receptor

Muscarinic acetylcholine receptor M1

Muscarinic acetylcholine receptor M2

Muscarinic acetylcholine receptor M3

Muscarinic acetylcholine receptor M4

Muscarinic acetylcholine receptor M5

Enzymes

Transporters

Multidrug resistance protein 1