Fluoxetine

C 17
H 18
F 3
N 1
O 1

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40 atoms, 41 bonds.

IUPAC name: N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine
Molar mass: 309.331(43) g/mol
Atoms: 40
SMILES: CNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F
InChIKey: RTHCYVBBDHJXIQ-UHFFFAOYSA-N
PubChem CID: 3386

Made of

C H F N O

Structural formula of fluoxetine. Each unlabelled corner is a carbon atom, and the 14 hydrogens on carbon are not drawn. It shows which atoms are joined to which, not the shape. The model above shows the shape.

Sold only on prescription, according to ChEMBL’s drug record, fluoxetine is an antidepressant of the class known as selective serotonin reuptake inhibitors, or SSRIs. LiverTox, NIDDK and NLM’s liver-injury database, describes its use against depression as widespread. Its molecule joins carbon, hydrogen, fluorine, nitrogen and oxygen in the formula C₁₇H₁₈F₃NO, with a molar mass of 309.33 g/mol.

ChEBI (Chemical Entities of Biological Interest) classes fluoxetine as an aromatic ether, with an oxygen atom linking a benzene ring to the rest of the molecule. Its parent in that description is 4-trifluoromethylphenol, whose OH hydrogen has given way to a 3-(methylamino)-1-phenylpropyl group. It is also a secondary amine, its nitrogen bonded to two carbons and one hydrogen.

The model draws this neutral parent molecule. In a 2004 list of antidepressants from the US Food and Drug Administration, the medicine appears as fluoxetine HCl, under the brand names Prozac and Sarafem. That form is the hydrochloride, this amine combined with hydrogen chloride.

Structure and bonding

Fluoxetine’s 40 atoms are arranged around one carbon that carries three arms besides its hydrogen. One arm is a benzene ring bonded straight to it, the second a ring held by an oxygen bridge, the third a two-carbon chain ending in NH–CH₃. On the second ring, opposite the oxygen, three fluorine atoms share a single carbon: the trifluoromethyl group of the name. The Labels button prints F on just those three atoms, and Space-filling merges them into one rounded cap at the ring’s outer edge.

Each ring shows three double bonds taking turns with three single ones. Yet the second electron pair of each double bond spreads, as in benzene, into rings of density above and below the ring’s plane. Computed, every ring C–C bond falls between 1.385 and 1.405 Å, whichever order is drawn. Turned edge-on in Stick, each ring is a flat hexagon, and Ball-and-stick shows the oxygen bridge bent at a computed 118.3°. The nitrogen is drawn neutral with an N–H bond, though amines are weak bases, as trimethylamine shows.

Where it turns up

The World Health Organization keeps fluoxetine on its Model List of Essential Medicines under depressive disorders and obsessive-compulsive disorder. The same list places it with three anxiety disorders, social anxiety, generalised anxiety and panic disorder, and with other common symptoms in palliative care. In the Anatomical Therapeutic Chemical (ATC) classification, the WHO’s coding of medicines, fluoxetine carries the code N06AB03. That code files it among nervous-system drugs, then among antidepressants, then with the SSRIs. A veterinary edition of the scheme, ATCvet, gives it QN06AB03 under the same SSRI heading.

The National Institute of Mental Health (NIMH) counts the SSRIs among the commonly prescribed antidepressants. They are chosen, NIMH explains, because they improve symptoms across a wide spread of depressive and anxiety disorders. NIMH adds that they come with fewer side effects than older antidepressants.

Why it matters

Fluoxetine was, in the words of Medical Subject Headings (MeSH), the first highly specific serotonin uptake inhibitor. ChEMBL dates its first approval as a medicine to 1987. The National Cancer Institute (NCI) describes it as a derivative of diphenhydramine.

In the drug classes of the US Food and Drug Administration (FDA), fluoxetine is a serotonin reuptake inhibitor. MeSH defines the SSRIs as compounds that specifically block the reuptake of serotonin in the brain. With reuptake blocked, NCI explains, serotonin accumulates in the synaptic space between nerve cells and its signalling strengthens. Over the long term the serotonin receptors grow less sensitive and fewer, a change NCI connects to the drug’s antidepressant, anti-anxiety, antiobsessional and antibulimic effects.

The body turns fluoxetine into other compounds, its metabolites. Among them are norfluoxetine and p-trifluoromethylphenol, the same phenol whose oxygen forms fluoxetine’s ether link. MeSH also files fluoxetine among the inhibitors of CYP2D6, an enzyme of the cytochrome P-450 family.

Properties

Properties of fluoxetine Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 3386.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₁₇H₁₈F₃NO
Molar mass	309.331(43) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	17
Hydrogen atoms	18
Fluorine atoms	3
Nitrogen atoms	1
Oxygen atoms	1
Bonds	41
Single bonds	35
Double bonds	6
PubChem molecular weight	309.33 g/mol	g/mol	PubChem

Safety

Fluoxetine carries a boxed warning, by NIMH’s account the most serious kind, which FDA announced for all antidepressants in October 2004. As FDA worded it then, antidepressants raised the risk of suicidal thinking and behaviour in children and adolescents who had major depressive disorder or other psychiatric disorders. In the United States, the 988 Suicide & Crisis Lifeline takes calls, texts and chats about anyone struggling or having thoughts of suicide, as NIMH describes it. Pure fluoxetine is also classed as fatal if inhaled and harmful if swallowed; the PubChem Laboratory Chemical Safety Summary for fluoxetine has the rest.

Questions

What is fluoxetine used for?

It is a prescription antidepressant of the class known as selective serotonin reuptake inhibitors (SSRIs). The World Health Organization lists it as an essential medicine for depressive disorders, obsessive-compulsive disorder, social anxiety disorder, generalised anxiety disorder and panic disorder, and for common symptoms in palliative care. The US National Cancer Institute credits it with anti-anxiety, antiobsessional and antibulimic activity alongside its antidepressant action.

Does fluoxetine contain fluorine?

Yes, three of its 40 atoms. Together with the carbon they share they form a trifluoromethyl group, CF₃, and ChEBI counts fluoxetine among the trifluoromethylbenzenes. In the 3D model each fluorine is joined to carbon by a single bond and carries no charge: the fluorine is not present as fluoride ions.

Why does fluoxetine have a black box warning?

The warning followed the US Food and Drug Administration's (FDA) combined analysis of short-term trials and a joint meeting of two FDA advisory committees on 13 and 14 September 2004, after which FDA directed the makers of every antidepressant to add it. FDA also judged a Medication Guide for patients appropriate. The National Institute of Mental Health reports the warning's later extension to adults through age 24.

What are the side effects of fluoxetine?

The US National Institute of Mental Health names upset stomach, headache and sexual dysfunction as frequent side effects of antidepressants, among them the selective serotonin reuptake inhibitors (SSRIs), fluoxetine's class. Medical Subject Headings (MeSH) describes fluoxetine's side effects as often more acceptable than those of traditional antidepressants. LiverTox, NIDDK and NLM's liver-injury database, records brief rises in blood levels of aminotransferase enzymes that cause no symptoms, and rare cases of acute liver injury that do.

Made of the same elements

C₃₃H₃₅FN₂O₅ Atorvastatin 76 atoms, 79 bonds.