FLUOXETINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H18F3NO.ClH
Molecular Weight	345.787
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CNCCC(OC1=CC=C(C=C1)C(F)(F)F)C2=CC=CC=C2

InChI

InChIKey=GIYXAJPCNFJEHY-UHFFFAOYSA-N

InChI=1S/C17H18F3NO.ClH/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20;/h2-10,16,21H,11-12H2,1H3;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C17H18F3NO
Molecular Weight	309.3261
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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 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. Fluoxetine is marketed under the trade names Prozac and Sarafem among others. It is also marketed for the treatment of premenstrual dysphoric disorder (Sarafem®, fluoxetine hydrochloride). PROZAC is a selective serotonin reuptake inhibitor indicated for: • Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years • Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years • Acute and maintenance treatment of Bulimia Nervosa in adult patients • Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients. Studies at clinically relevant doses in man have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine. Antagonism of muscarinic, histaminergic, and α1-adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressant (TCA) drugs. Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the tricyclic drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin transporter 135	Inhibitor 6523	Obsessive Compulsive Disorder	10.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major Depressive Disorder 68	Primary	Serotonin transporter	Approved 7109	PROZAC
Bulimia Nervosa 2	Primary	Serotonin transporter	Approved 7109	PROZAC
Obsessive Compulsive Disorder 4	Primary	Serotonin transporter	Approved 7109	PROZAC
Panic Disorder 17	Primary	Serotonin transporter	Approved 7109	PROZAC
[Obesity, Social anxiety disorder] 2			Approved (off-label) 8

PubMed

Title	Date	PubMed
Urinary retention with reboxetine-fluoxetine combination in a young man.	2000 Dec	11190365
Evidence of early onset of antidepressant effect in randomized controlled trials.	2001	11229783
The effects of antidepressants on sexual functioning in depressed patients: a review.	2001	11229450
Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.	2001	11229449
Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.	2001	11226678
Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness.	2001	11217873
Effects of selective serotonin reuptake inhibitors on sexual function.	2001 Apr	11270925
Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio.	2001 Apr	11270917
Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin.	2001 Apr	11270913
Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.	2001 Apr	11270912
Serotonergic manipulations both potentiate and reduce brain stimulation reward in rats: involvement of serotonin-1A receptors.	2001 Apr	11259559
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors.	2001 Apr	11255075
Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test.	2001 Apr	11182533
Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys.	2001 Apr	11182532
Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats.	2001 Feb	11273019
Characterization of 5-HT receptors in the parasitic nematode, Ascaris suum.	2001 Feb	11272652
Subjective and discriminative stimulus effects of two de-nicotinized cigarettes with different tar yields.	2001 Feb	11260814
Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment.	2001 Feb	11226808
Severe symptomatic hyponatremia during citalopram therapy.	2001 Feb	11217819
Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.	2001 Feb	11213850
Reversible galactorrhea and prolactin elevation related to fluoxetine use.	2001 Feb	11213313
Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers.	2001 Feb	11210405
Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo.	2001 Feb	11199947
Augmentation of fluoxetine's antidepressant action by pindolol: analysis of clinical, pharmacokinetic, and methodologic factors.	2001 Feb	11199945
The economic consequences of a drug-drug interaction.	2001 Feb	11199940
Dose-dependent seizure activity associated with fluoxetine therapy.	2001 Feb	11181988
Acute hypokalemic paralysis associated with long-term lithium therapy.	2001 Feb	11180215
Psychopharmacologic treatment of adolescent depression.	2001 Feb	11172238
Citalopram-induced bruxism.	2001 Feb	11157444
Female sexual dysfunction and antidepressant use.	2001 Feb	11156829
Fluoxetine and side effects in the geriatric population.	2001 Feb 1	11272295
A compulsive collecting behavior following an A-com aneurysmal rupture.	2001 Feb 13	11171910
Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK1 receptor antagonist.	2001 Feb 2	11166289
Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity.	2001 Feb 23	11263672
Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients.	2001 Jan	11225566
Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome.	2001 Jan	11204086
Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone.	2001 Jan	11202131
Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.	2001 Jan	11197585
Fluoxetine-induced Ca2+ signals in Madin-Darby canine kidney cells.	2001 Jan	11191831
Central 5-hydroxytryptamine-2A receptor expression in transgenic mice bearing a glucocorticoid receptor antisense.	2001 Jan	11174015
Fluoxetine in the treatment of Huntington's disease.	2001 Jan 1	11205429
No gender differences in placebo responses of patients with major depressive disorder.	2001 Jan 15	11164762
Fluoxetine (Sarafem) for premenstrual dysphoric disorder.	2001 Jan 22	11177220
Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice.	2001 Jan 31	11172895
Role of serotonin and noradrenaline in social dysfunction: a review of data on reboxetine and the Social Adaptation Self-evaluation Scale (SASS).	2001 Jan-Feb	11226552
Mutism: elective or selective, and acquired.	2001 Mar	11248456
Regulation of the vesicular monoamine transporter-2: a novel mechanism for cocaine and other psychostimulants.	2001 Mar	11181904
Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus.	2001 Mar 1	11169768
Modafinil does not affect serotonin efflux from rat frontal cortex synaptosomes: comparison with known serotonergic drugs.	2001 Mar 16	11251206
Adding group psychotherapy to medication treatment in dysthymia: a randomized prospective pilot study.	2001 Spring	11264333

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Bulimia Immediate-release oral formulations: Recommended dose: 60 mg orally once a day Usual Adult Dose for Depression Immediate-release oral formulations: Initial dose: 20 mg orally once a day, increased after several weeks if insufficient clinical improvement is observed Maintenance dose: 20 to 60 mg orally per day Maximum dose: 80 mg orally per day Delayed release oral capsules: Initial dose: 90 mg orally once a week, commenced 7 days after the last daily dose of immediate-release fluoxetine 20 mg formulations. Usual Adult Dose for Obsessive Compulsive Disorder Immediate-release oral formulations: Initial dose: 20 mg orally once a day, increased after several weeks if insufficient clinical improvement is observed. Maintenance dose: 20 to 60 mg orally per day Maximum dose: 80 mg orally per day Usual Adult Dose for Panic Disorder Immediate-release oral formulations: Initial dose: 10 mg orally once a day, increased after one week to 20 mg orally once a day Maintenance dose: 20 to 60 mg orally per day Maximum dose: 60 mg orally per day

Route of Administration: Oral

In Vitro Use Guide

Caco-2 SERT was also shown to be a high affinity (Kt=0.216 uM) saturable, Na(+) -dependent transporter that was inhibited by fluoxetine (IC(50)=17.6 nM).

Substance Class	Chemical Created by `admin` on `Tue Oct 22 00:22:44 UTC 2019` Edited by `admin` on `Tue Oct 22 00:22:44 UTC 2019`
Record UNII	I9W7N6B1KJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUOXETINE HYDROCHLORIDE

Official Name

English

LY-110140

Code

English

FLUOXETINE HYDROCHLORIDE [JAN]

Common Name

English

PROZAC

Brand Name

English

FONTEX

Brand Name

English

FLUNEURIN

Brand Name

English

LY110140

Code

English

FLUOXETINE HYDROCHLORIDE [EP]

Common Name

English

FOXETIN

Brand Name

English

FLUOX-PUREN

Brand Name

English

FLUOXETINE HCL

Common Name

English

FLUOXETINE HYDROCHLORIDE [MI]

Common Name

English

FLUOXETINE HYDROCHLORIDE [USAN]

Common Name

English

FLUXET

Brand Name

English

ADOFEN

Brand Name

English

FLUOXETINE HYDROCHLORIDE COMPONENT OF SYMBYAX

Common Name

English

FLUOXETINE HYDROCHLORIDE [HSDB]

Common Name

English

BENZENEPROPANAMINE, N-METHYL-.GAMMA.-(4-(TRIFLUOROMETHYL)PHENOXY)-, HYDROCHLORIDE (1:1)

Systematic Name

English

BENZENEPROPANAMINE, N-METHYL-.GAMMA.-(4-(TRIFLUOROMETHYL)PHENOXY)-, HYDROCHLORIDE, (+/-)-

Systematic Name

English

FLUOXETINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

RECONCILE

Brand Name

English

FLUOXETINE HYDROCHLORIDE [GREEN BOOK]

Common Name

English

SYMBYAX COMPONENT FLUOXETINE HYDROCHLORIDE

Common Name

English

FLUOXETINE HYDROCHLORIDE [WHO-DD]

Common Name

English

SARAFEM

Brand Name

English

(+/-)-N-METHYL-3-PHENYL-3-((.ALPHA.,.ALPHA.,.ALPHA.-TRIFLUORO-P-TOLYL)OXY)PROPYLAMINE, HYDROCHLORIDE

Common Name

English

FLUCTIN

Brand Name

English

LOVAN

Brand Name

English

FLUOXETINE (AS HYDROCHLORIDE)

Common Name

English

FLUSOL

Brand Name

English

FLUOXETINE HYDROCHLORIDE [VANDF]

Common Name

English

FLUOXETINE HYDROCHLORIDE [USP]

Common Name

English

FLUOXEREN

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94725