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Statements

Subject Item
n2:DB00472
rdf:type
n3:Drug
n3:description
Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). Fluoxetine is a racemic mixture of the R- and S- enantiomers and are of equivalent pharmacologic activity. 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 &alpha;- or &beta;-adrenergic, dopamine D<sub>2</sub> or histamine H<sub>1</sub> receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT<sub>1A</sub> and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT<sub>1A</sub> 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. Fluoxetine may be used to treat major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and in combination with olanzapine for treatment-resistant or bipolar I depression. Fluoxetine is the most anorexic and stimulating SSRI.
n3:dosage
n10:271B58E6-363D-11E5-9242-09173F13E4C5 n10:271B58E7-363D-11E5-9242-09173F13E4C5 n10:271B58E8-363D-11E5-9242-09173F13E4C5 n10:271B58E2-363D-11E5-9242-09173F13E4C5 n10:271B58E3-363D-11E5-9242-09173F13E4C5 n10:271B58E4-363D-11E5-9242-09173F13E4C5 n10:271B58E5-363D-11E5-9242-09173F13E4C5 n10:271B58DE-363D-11E5-9242-09173F13E4C5 n10:271B58DF-363D-11E5-9242-09173F13E4C5 n10:271B58E0-363D-11E5-9242-09173F13E4C5 n10:271B58E1-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Wong DT, Bymaster FP, Engleman EA: Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci. 1995;57(5):411-41. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/7623609 # Wong DT, Horng JS, Bymaster FP, Hauser KL, Molloy BB: A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 1974 Aug 1;15(3):471-9. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/4549929 # Carlsson A, Wong DT: Correction: a note on the discovery of selective serotonin reuptake inhibitors. Life Sci. 1997;61(12):1203. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9315511 # Gerber PE, Lynd LD: Selective serotonin-reuptake inhibitor-induced movement disorders. Ann Pharmacother. 1998 Jun;32(6):692-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9640489 # Caley CF: Extrapyramidal reactions and the selective serotonin-reuptake inhibitors. Ann Pharmacother. 1997 Dec;31(12):1481-9. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9416386
n3:group
approved
n3:halfLife
1-3 days [acute administration]; 4-6 days [chronic administration]; 4-16 days [norfluoxetine, acute and chronic administration].
n3:indication
Labeled indication include: major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and combination treatment with olanzapine for treatment-resistant or bipolar I depression. Unlabeled indications include: selective mutism, mild dementia-associated agitation in nonpsychotic patients, post-traumatic stress disorder (PTSD), social anxiety disorder, chronic neuropathic pain, fibromyalgia, and Raynaud's phenomenon.
n3:manufacturer
n4:271B58AB-363D-11E5-9242-09173F13E4C5 n4:271B58AC-363D-11E5-9242-09173F13E4C5 n4:271B58A1-363D-11E5-9242-09173F13E4C5 n4:271B58A2-363D-11E5-9242-09173F13E4C5 n4:271B589F-363D-11E5-9242-09173F13E4C5 n4:271B58A0-363D-11E5-9242-09173F13E4C5 n4:271B58A5-363D-11E5-9242-09173F13E4C5 n4:271B58A6-363D-11E5-9242-09173F13E4C5 n4:271B58A3-363D-11E5-9242-09173F13E4C5 n4:271B58A4-363D-11E5-9242-09173F13E4C5 n4:271B5899-363D-11E5-9242-09173F13E4C5 n4:271B589A-363D-11E5-9242-09173F13E4C5 n4:271B5897-363D-11E5-9242-09173F13E4C5 n4:271B5898-363D-11E5-9242-09173F13E4C5 n4:271B589D-363D-11E5-9242-09173F13E4C5 n4:271B589E-363D-11E5-9242-09173F13E4C5 n4:271B589B-363D-11E5-9242-09173F13E4C5 n4:271B589C-363D-11E5-9242-09173F13E4C5 n4:271B5895-363D-11E5-9242-09173F13E4C5 n4:271B5896-363D-11E5-9242-09173F13E4C5 n4:271B58B1-363D-11E5-9242-09173F13E4C5 n4:271B58B2-363D-11E5-9242-09173F13E4C5 n4:271B58AF-363D-11E5-9242-09173F13E4C5 n4:271B58B0-363D-11E5-9242-09173F13E4C5 n4:271B58B3-363D-11E5-9242-09173F13E4C5 n4:271B58A9-363D-11E5-9242-09173F13E4C5 n4:271B58AA-363D-11E5-9242-09173F13E4C5 n4:271B58A7-363D-11E5-9242-09173F13E4C5 n4:271B58A8-363D-11E5-9242-09173F13E4C5 n4:271B58AD-363D-11E5-9242-09173F13E4C5 n4:271B58AE-363D-11E5-9242-09173F13E4C5
owl:sameAs
n28:DB00472 n32:DB00472
dcterms:title
Fluoxetine
adms:identifier
n12:D00823 n13:63304-632-30 n16:203 n17:203 n18:46507902 n19:PA449673 n20:3386 n21:30130 n22:DB00472 n24:5118 n25:3269 n26:Fluoxetine
n3:mechanismOfAction
Metabolized to norfluoxetine, fluoxetine is a selective serotonin-reuptake inhibitor (SSRI), it blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT<sub>1A</sub> autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
n3:packager
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n3:patent
n30:6960577 n30:5910319
n3:routeOfElimination
The primary route of elimination appears to be hepatic metabolism to inactive metabolites excreted by the kidney. The S-enantiomer is eliminated more slowly and is the predominant enantiomer present at steady state.
n3:synonym
(+-)-N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine Prozac Fluoxétine Fluoxetina Fluoxetin (+-)-N-Methyl-3-phenyl-3-((alpha,alpha,alpha-trifluoro-P-tolyl)oxy)propylamine Fluoxetinum
n3:toxicity
Symptoms of overdose include agitation, restlessness, hypomania, and other signs of CNS excitation. LD<sub>50</sub>=284mg/kg (orally in mice). The most frequent side effects include: nervous system effects such as anxiety, nervousness, insomnia, drowsiness, fatigue or asthenia, tremor, and dizziness or lightheadedness; GI effects such as anorexia, nausea, and diarrhea; vasodilation; dry mouth; abnormal vision; decreased libido; abnormal ejaculation; rash; and sweating. Withdrawal symptoms include flu-like symptoms, insomnia, nausea, imbalance, sensory changes and hyperactivity.
n3:volumeOfDistribution
* 20-45 L/kg
n14:hasAHFSCode
n23:28-16-04-20
n3:foodInteraction
Take with food to reduce irritation and nausea. Avoid alcohol.
n3:mixture
n34:271B5840-363D-11E5-9242-09173F13E4C5
n3:proteinBinding
94.5% bound to human serum proteins, including albumin and alpha-1-glycoprotein.
n3:salt
n3:synthesisReference
Eduard Schwartz, Joseph Kaspi, Zinovi Itov, Gidon Pilarski, "Production of fluoxetine and new intermediates." U.S. Patent US5225585, issued October, 1990.
n6:hasConcept
n7:M0008635
foaf:page
n9:fluoxetine.htm n31:fluoxetine.html
n3:IUPAC-Name
n5:271B58ED-363D-11E5-9242-09173F13E4C5
n3:InChI
n5:271B58F3-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n5:271B58F2-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n5:271B58EF-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n5:271B58F0-363D-11E5-9242-09173F13E4C5
n3:SMILES
n5:271B58F1-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n5:271B5902-363D-11E5-9242-09173F13E4C5 n5:271B58EB-363D-11E5-9242-09173F13E4C5
n3:logP
n5:271B5904-363D-11E5-9242-09173F13E4C5 n5:271B58EC-363D-11E5-9242-09173F13E4C5 n5:271B58E9-363D-11E5-9242-09173F13E4C5
n3:logS
n5:271B58EA-363D-11E5-9242-09173F13E4C5
n14:hasATCCode
n15:N06AB03
n3:H-Bond-Acceptor-Count
n5:271B58F9-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n5:271B58FA-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n5:271B58F4-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n5:271B58F5-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n5:271B58F7-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n5:271B58F6-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n5:271B58F8-363D-11E5-9242-09173F13E4C5
n3:absorption
Well absorbed from the GI tract following oral administration. Oral bioavailability is estimated to be at least 60-80%. Peak plasma concentrations occur within 6-8 hours following a single oral administration of a 40 mg dose. The oral solution and delayed-release capsule are bioequivalent. Food does not affect the systemic bioavailability of fluoxetine but it delays the absorption by 1-2 hours (not clinically significant). Prozac Weekly capsules, a delayed–release formulation, contain enteric–coated pellets that resist dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. The enteric coating delays the onset of absorption of fluoxetine 1 to 2 hours relative to the immediate–release formulations.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
54910-89-3
n3:category
n3:containedIn
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n3:Bioavailability
n5:271B58FE-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n5:271B5900-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n5:271B5901-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n5:271B5903-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n5:271B58FD-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
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n3:Rule-of-Five
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n3:Traditional-IUPAC-Name
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n3:pKa--strongest-basic-
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