Appetite suppressing drugs fenfluramine

Despite its mechanistic complexity, the Hofmann rearrangement often gives high yields of both aryl- and alkylamines. For example, the appetite-suppressant drug phentermine is prepared commercially by Hofmann rearrangement of a primary amide. Commonly known by the name /cn-phen, the combination of phentermine with another appetite-suppressant, fenfluramine, is suspected of causing heart damage. 

The amphetamines were replaced by amphetamine analogs—substances somewhat less potent than amphetamines. Fen-Phen, the combination of fenfluramine and phentermine, was a popular appetite suppressant in the 1990s, but was associated with severe health problems such as pulmonary hypertension, heart valve dysfunction, and nerve damage. As a result, both drugs were withdrawn from the market. 

The noradrenergic drugs fenfluramine, dexfen-fluramine and phenteramine were formerly prescribed as appetite suppressants but were withdrawn when their use was associated with cardiac valve disease and pulmonary hjrpertension. 

The above study was based on information derived from the General Practice Research Database in the UK. Subjects who had been given at least one prescription for dexfenfluramine, fenfluramine, or phentermine after 1 January 1988, and who were 70 years or younger at the time of their first prescription were included. Subjects were considered to have a new cardiac abnormality if they had no history, on the basis of clinical records, of cardiac valvular abnormahties and if there was evidence of a new valvular disorder on the basis of echocardiography or chnical examination after exposure to appetite suppressants. All the data had been recorded before the pubhcation of recent reports of an association between appetite suppressants and cardiac valve disorders (25,27,30-32) or primary pulmonary hjq)ertension (14). Hence, it was possible to exclude the possibihty that enhanced awareness of possible serious adverse effects of appetite suppressants had led to closer surveillance of patients who were taking these drugs. Nevertheless, the study did not provide information on the frequency of idiopathic cardiac valve disorders that are asymptomatic or otherwise not chnicaUy diagnosed. 

Dexamphetamine is one of the most powerful and best known psychomotor stimulants, and other similar agents include dexfenfluramine. diethylpropion and fenfluramine. All these are on the controlled drugs list, and have a limited medical use as appetite suppressants. Such drugs work by interacting with the release of monoamines within the central (and peripheral) nervous system, and can be regarded as indirect SYMPATHOMIMEtics. Recently, there has been some use of the weak amphetamine-like stimulant methylphenidate to treat attention-deficient hyperactivity disorder (ADHD) in children. 

Anorectic drugs, appetite suppressants, are also found in diet pills such as fenfluramine (or fen-phen), phenter-mine, diethylproprion, and mazindol. Perhaps the most hazardous ingredient commonly found in diet pills until a few years ago was ephedrine. Ephedrine is more commonly known as one of the precursor chemicals needed to manufacture methamphetamine. 

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. 

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