Dexfenfluramine side effects

The newest appetite suppressant, sibutramine (Meridia), works by blocking the reuptake of both serotonin and norepinephrine. It does not stimulate nerve cells to release serotonin, as do fenfluramine and dexfenfluramine. Administered at 20 mg/ day, sibutramine effectively reduces weight in obese patients, but its use has not been assessed in eating disorder patients. The most common side effects of this medication are insomnia, dry mouth, and constipation. It has not been associated with the more serious heart and lung complications observed with fenfluramine and dexfenfluramine. Because sibutramine acts in part through modulation of norepinephrine, there is no rational basis for coadministering phentermine, which acts via this same mechanism. 

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. 

The principal side effects of phentermine are insomnia, restlessness, and euphoria. Some patients rapidly develop toleranee to this agent, resulting in discontinuation of therapy. The combination of phentermine with fenfluramine or dexfenfluramine was as-soeiated with inereased incidences of both primary pulmonary hypertension (PPH) and ear-diae valvulopathy, but it is unlikely that phentermine alone causes these same problems. Phentermine, nonetheless, contains a warning label listing PPH and cardiac valve lesions as possible adverse events. 

A number of compounds act either to suppress the activity of the hunger centre in the hypothalamus or to stimulate the satiety centre. Sometimes this is an undesirable side-effect of drugs used to treat disease and can contribute to the undernutrition seen in chronically ill people (section 8.4). As an aid to weight reduction, especially in people who find it difficult to control their food intake, drugs that suppress appetite can be useful. Three compounds are in relatively widespread use as appetite suppressants fenfluramine (and more recently the D-isomer, dexfenfluramine), diethylpropion and mazindol. The combination of phentermine and fenfluramine was withdrawn in the 1990s, after a number of reports associating it with cardiac damage. 

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. 

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