Fluoxetine

Category: pharmacological

Aliases: Prozac, Sarafem

Pharmacological Mechanism

Selective serotonin reuptake inhibitor — blocks SERT. Active metabolite norfluoxetine has 7–15 day t½, buffering missed doses + causing prolonged withdrawal. Weak 5-HT2C antagonism contributes to activation / norepinephrine release. CYP2D6 inhibitor (strong) — interaction-rich.

Half-Life (t½)

PO: 48h

Dosing Guidelines

PO: Typical 40 mg (Range: 20–80 mg)

Target Organ Systems

nervous
digestive

Interactions

St. John's Wort (contraindicated): Serotonergic overlap → serotonin syndrome; CYP induction also reduces SSRI levels. [Boyer 2005]
Desipramine (major): CYP2D6 inhibition (TDI). Preskorn 1994 (PMID:8195463) n=18 healthy males, DXM-phenotyped EMs, desipramine 50 mg/d × 7d alone then × 21d + fluoxetine 20 mg/d: desipramine Cmax 4.0×, AUC0-24 4.8× (vs sertraline 31%/23%). Ki ≈ 1/3.8 = 0.263 µM (lower-bound; TDI true Ki lower). Effect persists ~5 weeks post-fluox-discontinuation due to norfluoxetine.
Risperidone (warn): CYP2D6 inhibition. Bondolfi 2002 (PMID:11985287) n=11 psychotic inpatients (8 EM, 3 PM), risperidone 4-6 mg/d + fluoxetine 20 mg/d × 30d: parent AUC 83→345 ng·h/mL in EMs (4.15×), 398→514 in PMs. Active moiety (risperidone + 9-OH) only 470→663 (1.41×) since reduced 9-OH formation offsets parent rise. Ki ≈ 1/0.41 = 2.44 µM (active-moiety basis, the clinically-relevant endpoint).

Pathways It Modulates

BDNF / TrkB neurotrophic signaling (activator) — BDNF/TrkB (chronic, indirect via 5-HT)
Serotonin receptor pharmacology (inhibitor) — SERT
SSRI/SNRI discontinuation syndrome (inhibitor) — SERT (active metabolite norfluoxetine)

Chemical Identifiers

PubChem CID: 3386
Formula: C17H18F3NO
Molecular weight: 309.33 g/mol
InChIKey: RTHCYVBBDHJXIQ-UHFFFAOYSA-N
SMILES: CNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F