4 Fluoxetine

Fluoxetine hydrochloride (Prozac) is a widely prescribed antidepressant drug introduced by Eh Lilly Co in 1986 It differs from Compound A in having an —NHCH3 group in place of —N(CH3)2 What IS the structure of Prozac" ... 

Although each HPbC method has its own unique considerations, the following description of the determination of the fluoxetine in serum provides an instructive example of a typical procedure. 

Description of Method. Fluoxetine, whose structure is shown in Figure 12.31a, is another name for the antidepressant drug Prozac. The determination of fluoxetine and its metabolite norfluoxetine. Figure 12.31 b, in serum is an important part of monitoring its therapeutic use. The analysis is complicated by the complex matrix of serum samples. A solid-phase extraction followed by an HPLC analysis using a fluorescence detector provides the necessary selectivity and detection limits. 

If the peaks for fluoxetine and protriptyline are insufficiently resolved, how might you alter the mobile phase to improve their separation ... 

Fig. 3. Synthesis of fluoxetine (31). 3-ChIoro-I-phenyl-I-propanol reacts with sodium iodide to afford the corresponding iodo derivative, followed by reaction with methylamine, to form 3-(methyl amin o)-1-phenyl-1-propan 0I. To the alkoxide of this product, generated using sodium hydride, 4-fluorobenzotrifluoride is added to yield after work-up the free base of the racemic fluoxetine (31), thence transformed to the hydrochloride (51)...

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Selective Serotonin Reuptake Inhibitors. In 1987, the FDA approved fluoxetine [54910-89-3] (42) for use in the treatment of major... 

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

Azepindole Azipramine Cyclopenzapri ne Cycl indole Dothiepi n Fluotracen Fluoxetine Imafen... 

Fig. 2-16. The effect of organic modifiers on the resolution of fluoxetine enantiomers on vancomycin CSP (250 X 4.6 mm). The flow rate was 1.0 mL min at ambient temperature (23 °C). (Courtesy of Scott Sharpe, Eli Lilly Co.)...

More dramatic examples of how a change in chirality can affect the biological properties of a molecule are found in many drugs, such as fluoxetine, a heavily prescribed medication sold under the trade name Prozac. Racemic fluoxetine is an extraordinarily effective antidepressant but has no activity against... 

Fluoxetine, a heavily prescribed antidepressant marketed under the name Prozac, can be prepared by a route that begins with reaction between a phenol and an alkyl chloride. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

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