Fluoxetine | SSRI Antidepressant | CAS 54910-89-3

Product Name: Fluoxetine
CAS No.: 54910-89-3 (base)
Chemical Name: (±)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine
Molecular Formula: C₁₇H₁₈F₃NO
Appearance: White or almost white crystalline powder
Solubility: Fluoxetine hydrochloride is soluble in water and methanol
Stability: Relatively stable but sensitive to light
Stereochemistry: Racemic mixture of (R)- and (S)-enantiomers
Common salt: Hydrochloride

1. Introduction

Fluoxetine is an antidepressant from the selective serotonin reuptake inhibitor (SSRI) group. It increases serotonin concentration in the synaptic cleft. It is used for the treatment of depression, obsessive-compulsive disorder, and bulimia.

Fluoxetine, better known under the brand name Prozac®, was one of the first representatives of the SSRI class and revolutionized the treatment of depressive disorders due to its efficacy and better tolerability profile compared to tricyclic antidepressants. Its mechanism of action is based on selective blockade of serotonin reuptake, leading to enhanced serotonergic transmission in the central nervous system.

2. Chemical Structure & Synthesis

Fluoxetine is synthesized in several stages. One approach involves the Mannich reaction between 3-chloropropiophenone, methylamine, and formaldehyde, followed by reduction of the keto group and reaction of the resulting amino alcohol with 4-chlorobenzotrifluoride in the presence of a base. It is often used as the hydrochloride salt.

3. Mechanism of Action

Fluoxetine selectively inhibits presynaptic serotonin (5-hydroxytryptamine, 5-HT) reuptake in brain neurons. This leads to an increase in serotonin concentration in the synaptic cleft and prolongation of its action on postsynaptic receptors. Unlike tricyclic antidepressants, fluoxetine has low affinity for muscarinic, histaminergic, and α-adrenergic receptors, resulting in fewer side effects associated with blockade of these receptors.

4. Pharmacokinetics

Well absorbed from the gastrointestinal tract. Food intake does not significantly affect absorption. Intensively metabolized in the liver (via CYP2D6 and CYP2C19) by N-demethylation to the active metabolite norfluoxetine, which is also an SSRI. Fluoxetine and norfluoxetine have long half-lives (fluoxetine – several days; norfluoxetine – 7–15 days), providing stable concentrations with regular use but also requiring a long time to reach steady-state concentration and complete elimination. Excreted primarily by the kidneys.

5. Applications

• Depressive disorders of varying severity (particularly effective for depression with anxiety and apathy)

• Obsessive-compulsive disorder (OCD)

• Bulimia nervosa – as part of comprehensive psychotherapy to reduce the frequency of binge eating and vomiting episodes

• Panic disorder with or without agoraphobia

• Premenstrual dysphoric disorder (PMDD)

6. Conclusion

Fluoxetine is an effective and widely used antidepressant from the SSRI group that has significantly improved the quality of life of many patients with depression and other psychiatric disorders. Its relatively favorable side effect profile compared to TCAs and convenient once-daily dosing have contributed to its popularity. However, like other antidepressants, fluoxetine can cause side effects and requires individual dose selection under medical supervision.