Fenfluramine Redux side effects

The amphetamine analogue fenfluramine, whose synthesis you designed while you were reading Chapter 31, used to be marketed as an anorectic (appetite-suppressant)—it stimulates the production of the hormone serotonin and makes the body feel satisfied—until it became clear that some undesirable side-effects could be avoided by administering it solely as the (S)-enantiomer. Fenfluramine relaunched as the enantiomerically pure dexfenfluramine, and was reputedly a turning point for your overweight patients —was available in the USA as a component of the slimming pill Redux. 

New pharmacological treatments have been developed for the treatment of obesity. These include the combination of phentermine and fenfluramine (phen-fen) and, alternatively, dexfenfluramine (Redux). Phentermine (Fastin, lonamin) is a stimulant and fenfluramine (Pondimin) is a serotonin agonist. In combination they have persistent appetite suppression and weight loss effects. These medications can cause anxiety and insomnia and must be used with extreme caution if taken with antidepressants, especially SSRIs. Dexfenfluramine works similarly, but avoids the side effect of increased anxiety, and instead tends to cause diarrhea, dry mouth, and somnolence. There have also been reports of pulmonary hypertension, a potentially fatal condition, especially when taken for longer than three months. Some researchers (Ricuarte et al. 1991 McCann et al. 1994) have expressed concern because rats given these medications showed evidence of neuronal toxicity. Thus, they are effective medications, but must be used with caution. 

S)-(+) Dexfenfluramine (Redux ) 21, a serotonin reuptake inhibitor, has been marketed in Europe and the United States as a very effective anti-obesity drug. This isomer, obtained by resolution of racemic fenfluramine using d-camphoric acid, exhibits a greater anorectic effect than die (R)-(-) and racemic forms, since it is more selective on serotonin as a 5-HT agonist (22). As a result of reports of imdesirable side effects, e.g., valvular heart disease, Redux has been wididrawn from the market, while further studies continue. Racemic fluoxetine (Prozac ) (22) is widely used for treatment of major depression and is one of the most commonly prescribed medications. It is also approved for treatment of obsessive compulsive disorder and bulimia. Non-racemic fluoxetine and its intermediates have been prepared by chemical, enzymatic. 

---