Fluoxetine chemical structure

Talopram 58 and citalopram 59 (Figure 2.17) are closely related in their chemical structures. Nevertheless, talopram is a norepinephrine uptake blocker with a selectivity factor of about 550 against serotonin uptake, whereas citalopram is a serotonin uptake blocker, with a selectivity of 3400 against norepinephrine uptake. A similar selectivity difference applies to the even more closely related pair nisoxetine 60, with a norepinephrine uptake selectivity of about 180, and fluoxetine 61 (Figure 2.17), with a serotonin uptake selectivity of 54 [33],... 

The diversity of the SSRIs is evident not only in their chemical structures, but also in their pharmacokinetic profiles. Fluoxetine has an elimination half-fife of 2 to 3 days (4 to 5 days with multiple dosing). The single-dose hah-hfe of norfluoxetine, the active metabolite, is 7 to 9 days. Paroxetine and sertrahne have half-lives of approximately 24 hours. Unlike paroxetine, sertraline has an active metabolite, but the metabohte contributes minimally to the pharmacologic effects. Escitalopram has a half-life of approximately 30 hours. Peak plasma concentrations of citalopram are observed within 2 to 4 hours after dosing, and the elimination half-life is about 30 hours. The SSRIs, with the exception of fluvoxamine, escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%). The SSRIs are extensively distributed to the tissues, and aU, with the possible exception of citalopram, may have a nonlinear pattern of drug accumulation with long-term administration. ... 

There are several SSRI inhibitors. Their chemical structures are different but they have similar modes of action, namely binding to the SERT. However, they have different pharmacokinetic parameters such as half-life, and differences in adverse effects and drug interactions [54]. Fluoxetine was the first drug of the class, approved in the U.S. in 1987. It is a chiral molecule and the racemic mixture is used as the hydrochloride salt (Prozac , Lilly). It has been approved and marketed in more than 90 countries and used by more than... 

Figure 2.17 The structural analogs talopram 58 and citalopram 59 (upper compounds), as well as nisoxetine 60 and fluoxetine 61 (lower compounds), are chemically closely related. Whereas 58 and 60 (left compounds) are highly selective norepinephrine uptake inhibitors (selectivity factors of 550 and 180, respectively), the close analogs 59 and 61 (right compounds) are selective serotonin uptake inhibitors (selectivity factors of 3400 and 54, respectively).

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