Fluoxetine reactions

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)...

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. 

Adverse reactions with administration of bupropion include citation, dry mouth, insomnia, headache, nausea, constipation, anorexia, weight loss, and seizures. Fluoxetine administration may result in headache, activation of mania or hypomania, insomnia, anxiety, nervousness, nausea, vomiting, and sexual dysfunction. Trazodone administration may cause the following adverse reactions drowsiness, skin disorders, anger, hostility, anemia, priapism, nausea, and vomiting. Additional... 

There is a decreased effectiveness of fluoxetine in patients who smoke cigarettes during administration of die drug. Fluoxetine is not administered witii lithium because this combination can increase lithium levels. The SSRIs are not administered witii herbal preparations containing St. Jbhn s wort because tiiere is an increased risk for severe reactions. 

Lam MW, CJ Young, SA Mabury (2005) Aqueous photochemical reaction kinetics and transformation of fluoxetine. Environ Sci Technol 39 513-522. 

Tomoxetine and fluoxetine are antidepressants. Both enantiomers of each compound can be prepared enantiospecifically starting from cinnamyl alcohol. Give a reaction sequence that will accomplish this objective. 

A major challenge to the development of new drugs is the discovery of new therapeutic targets. For example, the phenomenal success of fluoxetine (Prozac ) has been due to the fact that it was the first selective serotonin re-uptake inhibitor approved for world market release, combined with its improved adverse drug reaction profile. However, no new classes of antidepressants have emerged in recent years. 

Fig. 19.1 Differential displays comparing RNAs from saline (S)-, imipramine (I)- or fluoxetine (F)-treated rats. Total RNA was extracted from hypothalami of animals treated with the different drugs for two months. Autoradiograms of amplified -[35S]-dATP-labeled PCR (polymerase chain reaction) products after electrophoresis in 6% polyacrylamide gels are shown for two different primer combinations that identified one upregulated (arrowhead) and one downregulated (arrow) fragment in the groups treated with antidepressants (from [4] with permission).

An extensive study was undertaken to optimize the carbonyl-ene reaction between benzaldehyde (143, Scheme 30) and 3-methylene-2,3-dihydrofuran 144, which was utilized in the enantioselective synthesis of fluoxetine hydrochloride, a selective seratonin reuptake inhibitor.89 The degree of hydration of the molecular sieves proved important in the stereoselectivity of the reaction, with lower enantioselectivities reported both with highly active... 

Additional ADRs linked to diet pills include psychosis myocardial ischemia drug interactions, such as the interaction of fenfluramine with imipramine, fenfluramine with amitriptyline or desipramine, or the toxic reaction between fluoxetine and phentermine and the release of serotonin while inhibiting its reuptake, contributing to hyperserotonin reactions. When the next craze takes hold of patients and their physicians, hopefully physicians and pharmacists will take a more vocal position and recommend restraint, xmtil some proof of efficacy and lack of toxicity is shown for new faddish off-label combinations. 

Bostwick, J.M. and Brown, T.M., A toxic reaction from combining fluoxetine and phentermine, /. Clin. PsychopharmacoL, 16,189-190,1996. 

The bioreduction of carbonyl compounds with reductases has been exploited for many years, especially in the case of ketones, with baker s yeast Saccharomyces cerevisiae) being the most popular biocatalyst [45]. For instance, yeast treatment of 3-chloropropiophenone affords the expected (lS)-3-chloro-l-phenylpropan-l-ol, which was treated with trifluorocresol in tertrahydrofuran in the presence of tri-phenylphosphine and diethyl azodicarboxylate at room temperature to give (3R)-l-chloro-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propane and the later reaction with methylamine leads to (R)-fluoxetine that is an important serotonin uptake inhibitor (Scheme 10.19) [46]. 

Fluoxetine Fluoxetine, 3-[p-(trifluoromethyl)-phenoxy]-N-methyl-3-phenylpropylamine (7.3.6), is synthesized by reaction of p-trifluoromethylphenol with 3-(chloro)-N-methyl-3-phenylpropylamine in the presence of potassium carbonate [59,60]. 

Special populations Use a starting dose of 6 mg/25 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine/fluoxetine (eg, female gender, elderly, nonsmoking status). When indicated, perform dose escalation with caution in these patients. Olanzapine/fluoxetine has not been systemically studied in patients older than 65 years of age or in patients younger than 18 years of age. 

Venlafaxine, although its re-uptake inhibitory activity is not restricted to serotonin, is often classified as an SSRI because of its similar spectrum of adverse reactions. It has a short elimination half-life in contrast to the other serotonin re-uptake inhibitors. Fluoxetine, norfluoxetine and paroxetine are inhibitors of their own metabolism by CYP2D6 resulting in non-linear pharmacokinetic behavior. 

Adverse reactions include nausea, nervousness, headache, insomnia, anxiety. Sexual dysfunction with loss of libido is a common complaint. Insomnia can be a problem. Urticaria and rashes have been described. Venlafaxine may significantly increase the risk of suicide and is therefore not recommended as a first line treatment of depression. The view that also fluoxetine and other SSRIs can lead to suicide is under debate for quite some time now. In most countries SSRIs are not approved for use in pediatric populations. In the UK and in the USA only fluoxetine can be prescribed for children. 

SSRIs and similar drugs (e.g., citalopram, fluoxetine, fluvoxam-ine, paroxetine, sertraline) Stimulation of 5-HT receptors Increased serotonergic effects and increased likelihood of adverse reactions (e.g., serotonergic syndrome) Avoid concurrent use... 

Steiner W, Eontaine R Toxic reaction following the combined administration of fluoxetine and L-tryptophan five case reports. Biol Psychiatry 21 1067-1071,... 

The clinical and commercial success of the antidepressant compound fluoxetine (Chapter 2 Prozac) engendered considerable work in other laboratories. A benzo-dioxan based compound that shows similar activity shares only a few stmctural features with the prototype. The benzodioxan nucleus (68-3) is formed by an alkylation reaction between the fluorocatechol (68-1) and the derivative (68-2) from meso, and hence achiral, butanetetrol. The benzyl protecting groups are then removed by hydrogenation over palladium, and the thus-obtained diol is converted to the fiii-toluene-sulfonate (68-4) by reaction with toluenesulfonyl chloride. Treatment of that intermediate with benzylamine leads to fiw-alkylation on the same nitrogen to form a pyrrolidine ring and thus the tricyclic compound (68-5). A second hydrogenolysis step then leads to fluparoxan (68-6) [70]. 

The clinician must also be aware of the long half-life (several days) of fluoxetine because the potential for this reaction remains present until its active metabolite, norfluoxetine, has been cleared. This can take 6 weeks or more depending on the daily dose of fluoxetine that has been used, as well as the age and health of the patient. 

The procedure for getting the polymer-bound ligands is very easy to reproduce. Three jS-functionalized aromatic ketones were successfully reduced to the corresponding alcohols by heterogeneous asymmetric hydrogen transfer reaction with formic acid-triethylamine azeotrope as the hydrogen donor. One of the product alcohols (19c) is an intermediate for the synthesis of optically active fluoxetine. 

Wirth DD, Baertschi SW, Johnson RA, et al. Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine. J Pharm Sci 1998 87(1) 31 39. 

Molloy and Schmiegel described the original synthetic route to fluoxetine (4) (Scheme 1). Mannich reaction of acetophenone (7) yielded the aminoketone 8. 

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