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http://beta.aalf.org/wiki/index.php?title=SmithsonPerry664&action=history Revision history for this page on the wiki en MediaWiki 1.13.3 Sun, 01 Nov 2026 05:02:12 GMT http://beta.aalf.org/wiki/index.php?title=SmithsonPerry664&diff=10422&oldid=prev <p>New page: Fluoxetine (trade name Prozac) is one of the many generally recommended pharmaceuticals in the United States. In the year 2007, more than 22.2 million prescriptions had been disp...</p> <p><b>New page</b></p><div> Fluoxetine (trade name Prozac) is one of the many generally recommended pharmaceuticals in the United States. In the year 2007, more than 22.2 million prescriptions had been dispensed for Prozac or perhaps one of its many general equivalents. Introduced in 1987 by the Eli Lilly Company, Prozac is used to deal with a number of psychotropic disorders such as major depression and also obsessive-compulsive disorder (FDA 7-9).<br /> Fluoxetine’s IUPAC name is N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine. This name reflects the molecule’s practical groups - a particular ether, a secondary amine, two phenyls, as well as three alkylfluorides. <br /> In addition to possessing many different functional groups, fluoxetine additionally contains seven different types of covalent bonds. These include very stable bonds such as the conjugated carbon-to-carbon double bonds of the phenyl groups and fairly unstable bonds such as the carbon-to-nitrogen single bonds of the amine. <br /> Fluoxetine has received a Chemical Abstracts Service registry number of 54910-89-3. Its molecular formula is C17H18F3NO, and its molar mass is 309.33 g/mol (O’Neil 4185). Under standard laboratory conditions, Fluoxetine is a white to off-white crystalline strong. Pure samples display a melting aim of 158.4-158.9 degrees Celsius. With a maximum aqueous solubility of 14 mg/mL, fluoxetine is practically insoluble in water. Fluoxetine’s LD50 for mice is 248 mg/kg, as well as for rats it is 452 mg/kg (O’Neil 4185).<br /> Fluoxetine’s third carbon is the substances only stereogenic center. For this cause, the two structures seen on the following page in figure 4 are the substances only 2 enantiomers. <br /> Healing preparations of fluoxetine are racemic mixtures of (R)-fluoxetine and (S)-fluoxetine. Both enantiomers are highly specific as well as potent serotonin reuptake inhibitors; however, (S)-fluoxetine is eliminated from the body much more gradually compared to its (R) counterpart. For this reason, the predominant enantiomer found in blood plasma is (S)-fluoxetine (FDA 2). <br /> Several multiplets (a) are present in the 7.0-7.8 ppm region. These signals match to the protons of the 2 aromatic rings. A triplet (b) can be seen at 5.20 ppm. This downfield signal corresponds to the highly deshielded proton of the 3rd carbon on fluoxetine’s aliphatic carbon string. A second triplet (c) is found at 2.68 ppm. This signal corresponds to the 2 protons of the first carbon of the substances aliphatic carbon string. The singlet (d) appearing at 2.43 ppm corresponds to the three protons of the amine’s methyl group. Finally, the doublet of triplets (e) at 2.07 ppm corresponds to the protons of the second carbon of fluoxetine’s aliphatic carbon cycle. <br /> Fluoxetine’s IR spectrum likely contains a medium peak at 3500 cm-1 related to N-H stretching of the secondary amine. Aromatic C−H stretching likely occurs as a powerful, sharp peak at 3150-3050 cm-1. A powerful, sharp peak corresponding to aliphatic Csp3−H stretching should be visible at 3000-2850 cm-1. As can really be seen in figure 6, aromatic C=C stretching appears as a series of sharp, medium-to-strong peaks between 1600 and also 1400 cm-1. Also, stretching of the C-O bonds of the ether produce a powerful, sharp signal at 1300 cm-1. Finally, the 3 C-F bonds can be seen because strong signals between 1400 cm-1 and 1000 cm-1 (Pavia, Lampman, Kriz, and Engel 851). <br /> Whilst several viable syntheses exist for fluoxetine, one synthesis is especially suited for undergraduate laboratories. Whilst a couple syntheses use toxic compounds such as the reducing agent diborane (B2H6) and the chlorinating agent thionyl chloride (SOCl2) to give fluoxetine, there is at least one synthesis that circumvents these hazardous reagents. The synthesis given by Perrine, Sabanayagam, and Reynolds instead uses the less hazardous reagents sodium borohydride (NaBH4) and also potassium tert-butoxide (KOC[CH3]3). Furthermore, while other syntheses need use of the very expensive substance 4-(trifluoromethyl)phenol, this synthesis avoids the compound as well as rather utilizes the inexpensive chemical 1-chloro-4-(trifluoromethyl)benzene. For these reasons, the synthesis given in figure 7 is ideal suited for introductory organic chemistry laboratories. <br /> The commercially available element 3-(dimethylamino)-1-phenylpropan-1-one (1) is reduced with sodium borohydride (NaBH4) to form 3-(dimethylamino)-1-phenylpropan-1-ol (2). This secondary alcohol is deprotonated with potassium tert-butoxide (KOC[CH3]3) and undergoes aromatic substitution onto 1-chloro-4-(trifluoromethyl)benzene (3) via the reduction of a chloride ion. This aromatic substitution occurs inside the polar aprotic solvent DMAA and subsequently yields the drug precursor “N-methyl-Prozac” (4). NMP is converted to Prozac (fluoxetine, 5) through N-demethylation with cyanobromide (CNBr). <br /> Fluoxetine’s main activity and system of action in vivo is as a selective [ http://www.squidoo.com/serotonin2 serotonin] reuptake inhibitor (SSRI). Serotonin, 5-hydroxytryptamine (5-HT), is a neurotransmitter associated with the mental sensation of well-being. In healthy neurons, 5-hydroxytryptamine is synthesized from the amino acid tryptophan through catalysis by tryptophanhydroxylase (TH) and aromatic aminoacid decarboxylase (AADC). Newly generated serotonin is stored in vesicles in the axon port and then released into the synaptic space. The freed serotonin molecules activate 5-HT receptors on the adjacent dendrites. Over the years, the serotonin in the synaptic room is either degraded by monoamine oxidase or accumulated by the 5-HT transporters on the axon. In the second case, the serotonin is located in vesicles and reused. A significant contributing factor to major depression is the overactive reuptake of serotonin. If the 5-HT transporters remove serotonin too quickly, neurological imbalances including depression can happen. Fluoxetine as well as other selective serotonin reuptake inhibitors block a portion of the 5-HT transporters as well as increase the serotonin available to the dendritic 5-HT receptors. This mechanism of selectively inhibiting serotonin reuptake can restore neurological balance and lower the symptoms of depression (Wong, Perry, and Bymaster 767).<br /> In addition to the above model, a new non-SSRI system of action for fluoxetine has been discovered by medicinal chemists. In 2006, Pinna and also co-workers reported that fluoxetine and also its N-desmethyl congener norfluoxetine selectively increase brain neurosteroid content at doses inadequate to inhibit serotonin reuptake. Pinna believes that fluoxetine’s pharmacologic actions would certainly be described more accurately as a “selective brain steroidogenic stimulant.” This pharmacology is consistent with neurosteroids’ known involvement in human mind pathophysiology, such as major depression, postpartum depression, post-traumatic strain disorder, and different anxiety disorders (Daniels 1039). Consequently, Prozac’s health effects seem to be extracted from not just its capability to selectively restrict serotonin reuptake, however also its capability to increase mind neurosteroids.<br /> Fluoxetine is indicated for several psychotropic disorders. The drug’s most common indication is for the treatment of major depressive disorder in adults. This disorder is characterized by a prominent and also persistent depressed or dysphoric mood that significantly affects the ability of the individual to function. Depression in children and adolescents has also been effectively treated with Prozac (FDA 7-8).<br /> An additional indication for this prominent antidepressant is within the treatment of obsessive-compulsive disorder. Individuals with this disorder suffer from obsessions or compulsions that cause marked distress, consume wide amounts of time, or interfere significantly with day-to-day activities. Prozac’s effectiveness in the treatment of OCD has been firmly established via 13-week tests with adults and with pediatric patients. Fluoxetine is also indicated to deal with bulimia nervosa. Bulimia, a behavioral disorder characterized by binge eating and subsequent purging, has been treated effectively with Prozac. Other uses for this SSRI include the treatment of panic disorders and premenstrual dysphoric disorder (FDA 8-9). <br /> Because of the fairly low incidence of adverse effects, fluoxetine has gained popular use in the previous twenty many years. However, a very few adverse effects should be noted. These effects include nausea (24% incidence), nervousness, insomnia (15% incidence), sedation, headache, dizziness, dry mouth, diarrhea, constipation, perspiration, tremor, anorexia, as well as erectile dysfunction. Occurring in 3% if individuals, rashes signal a possibly serious side effect and also warrant immediate discontinuation of the medication. Total, approximately 15% of just about all patients recommended fluoxetine will discontinue its utilize due to adverse side effects (Stokes 1191).<br /> Fluoxetine is contraindicated in a very few important situations. This pharmaceutical is not to be recommended to any kind of patient with a known allergy to SSRI’s. Because SSRIs can result life-threatening hypersensitive responses, treatment should really be immediately discontinued if the individual develops a rash. Possibly deadly reactions have also happened with concomitant use of monoamine oxidase inhibitors, thioridazine, or pimozide with fluoxetine. Therefore, people really should discontinue use of these medications at least two weeks before taking the first dose of fluoxetine. Also, fluoxetine should be discontinued at least five weeks prior to beginning treatment with either monoamine oxidase inhibitors, thioridazine, or pimozide with fluoxetine (NIH 3). Herbal medications like St. John’s wort or perhaps tryptophan should be avoided whilst taking fluoxetine. Because both of these over-the-counter medications increase serotonin levels, a serious condition known because [http://hurbestblog.ucoz.com/ serotonin syndrome] can occur (Mayo 3). In addition, taking fluoxetine by expecting mothers has been shown to prove damaging to unborn infants. A case study published in 2006, showed that babies whose moms took SSRIs after the twentieth week of pregnancy were much more likely to have persistent pulmonary hypertension (PPHN), a a result of morbidity in infants (FDA).<br /> Whenever fluoxetine was introduced in 1987, it enabled a monumental step forward in the<br /> treatment of depression. Fluoxetine treats depression more effectively than its predecessors with greatly fewer and also much more benign side effects. Due to the ease of once-a-day dosing and a relatively low side effect profile, patient consent is high with fluoxetine (Stokes 1224). A truly revolutionary treatment for mood disorders, fluoxetine is a pharmaceutical drug the authors would readily prescribe for patients suffering from major depression, obsessive-compulsive disorder, or perhaps other emotional conditions related to serotonin imbalance.<br /> Functions Mentioned<br /> Daniels, R. Nathan and Craig Lindsley. “A Brand new, Non-SSRI System of Action for Prozac.”<br /> Current Subjects in Medicinal Chemistry 7 (2007): 1039.<br /> Food and Drug Administration. Prozac. Feb. 2004. 22 Mar. 2011&lt;http://www.fda.gov/ohrms/<br /> dockets/ac/04/briefing/4006B1_05_Prozac-label.pdf&gt;.<br /> “Information for Medical Professionals: Fluoxetine (marketed as Prozac)”. Jul. 2006. 07 <br /> Apr. 2011&lt; http://alturl.com/vbvkp&gt;.<br /> Lide, David R. CRC Handbook of Chemistry and Physics: a Ready-reference Book of Chemical and Physical Data: 2008-2009. 90th ed. Boca Raton: CRC, 2009.<br /> Mayo Clinic Staff members. “Selective Serotonin Reuptake Inhibitors.” Mayo Clinic News. Dec. 2010.<br /> 25 March 2011 &lt;http://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=<br /> medlineplus&amp;query=prozac&amp;x=12&amp;y=16.html<br /> National Institute of Health. Fluoxetine. March 2011. 22 Mar. 2011&lt;http://www.nlm.nih.gov/<br /> medlineplus/druginfo/meds/a689006.html&gt;.<br /> O’Neil, Maryadele, Patricia Heckelman, Cherie Koch, as well as Kristin Roman, eds. The Merck<br /> Index. 14th ed. Whitehouse Station: Merck Research Laboratories, 2006.<br /> Pavia, Donald L., Gary M. Lampman, George S. Kriz, and Randall G. Engel. Introduction to Organic Laboratory Techniques: a Microscale Approach. Belmont: Thomson Brooks/Cole, 2007.<br /> Perrine, Daniel M., Nathan R. Sabanayagam, and also Kristy J. Reynolds. “The Synthesis of NMP, a Fluoxetine (Prozac) Precursor, in the Introductory Organic Laboratory.” In the Laboratory: Notes for the Instructor.<br /> Stokes, Peter E. and Aliza Holtz. “Fluoxetine Tenth Anniversary Update: The Progress<br /> Continues.” Medical Therapeutics 19 (1997): 1137-1250.<br /> Wong, David T., Kenneth W. Perry, and also Frank Porter Bymaster. &quot;Access: The Discovery of Fluoxetine Hydrochloride (Prozac): Nature Ratings Drug Discovery.&quot; Nature Publishing Group: Science Journals, Jobs, and Information. Web. 10 Mar. 2011.</div> Thu, 23 Feb 2012 19:17:27 GMT SmithsonPerry664 http://beta.aalf.org/wiki/index.php?title=Talk:SmithsonPerry664