Appetite suppressing drugs phentermine

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 appetite-suppressing effect of (3-phenylethylamine drugs is either related to their sympathomimetic effect (metamphetamine, phentermine, diethylpropion), to... 

Older drugs still available in some countries include phenylpropanolamine, benzphetamine, amphetamine, methamphetamine, phentermine, diethylpropion, mazindol, and phendimetrazine. These drugs are all amphetamine mimics and are central nervous system appetite suppressants they are generally helpful only during the first few weeks of therapy. Their toxicity is significant and includes hypertension (with a risk of cerebral hemorrhage) and addiction liability. 

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 As a result, both drugs were withdrawn from the market.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 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. 

The adverse effects of amphetamine and related sympathomimetic appetite suppressants are well documented. All of these agents are classified by the U.S. Drug Enforcement Administration (DEA) as controlled substances (classes II-IV) according to their potential for causing addiction (see Table 15.4). Class II agents such as amphetamine are highly abused, with prescription restricted to speeial circumstances class TV anorectic drugs such as sibutramine, phentermine, di-ethylpropion, and mazindol have minimal abuse potential. 

Nevertheless, phentermine, from SmithKUneBeecham, became the first appetite suppressant (anorectic), which was approved by the FDA in 1959 (Fig. 5.106). [243] Phentermine leads to increased release of catecholamines like dopamine, adrenaline (epinephrine) and noradrenaline (norepinephrine), which reduce the sensation of hunger. However, the effect declines in the course of several weeks. Due to grave side-effects (sleeplessness, nervousness, nausea, obstipation. Angina pectoris problems and acute psychoses) the drug has meanwhile been withdrawn from a number of markets. 

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. 

CNS stimulants can be classified as Psychomotor stimulants compounds that display a stimulatory effect primarily on brain functions and which activate mental and physical activity of the organism. They are made up of methylxanthines (caffeine, theophylline, pentoxifyllin), amphetamines (dextroamphetamine, methamphetamine), and also methylphenidate and pemoline. Respiratory stimulants or analeptics compounds, which cause certain activations of mental and physical activity of the organism, and primarily excite the vasomotor and respiratory centers of the medulla (doxapram, almitrine).Drwgi that suppress appetite or anorectics drags that activate mental and physical activity of the organism, but primarily accentuate the excitatory center of satiation in the hypothalamus (phentermine, diethylpropion).In order to increase mental capability, nootropics — drugs that increase the functional state of the brain — are sometimes used, the effect of which is associated with blood flow and metabolism of the brain. 

---