Appetite suppressing drugs

Griffiths, RR. Brady, J.V. and Snell, J.D. Relationship between anorectic and reinforcing properties of appetite suppressant drugs Implieations for assessment of abuse liability. Biol Psychiatry 13 283-290, 1978. 

Y )- Benzyl morpholine is a potent appetite suppressant drug. The synthesis of 2-(/ )-benzyl-morpholine began with the reduction of the unsaturated bromocinnamaldehyde to the corresponding saturated (X)-bromo-alcohol by baker s yeast, with a very low ee of 63%. However, an efficient transformation can be achieved by controlling the substrate concentration with the addition of hydrophobic resin Amberlite XAD-1180 [26]. With a resin-to-substrate ratio of one and an initial substrate concentration of 5 gL, the saturated (X)-bromo-alcohol was recovered at nearly quantitative yield and 98.6% ee. 

Besides behavior and blood pressure, catecholamine neurons also have important roles in other brain functions. Regulation of neuroendocrine function is a well-known action of catecholamines for example, DA agonists reduce serum prolactin concentration, especially in conditions of hypersecretion. Ingestive behavior can be modulated by brain catecholamines, and some appetite-suppressing drugs are believed to act via catecholaminergic influences. Catecholamines also participate in regulation of body temperature. 

Khan MA, Herzog CA, St Peter TV, Hartley GG, Madlon-Kay R, Dick CD, Asinger RW, Vessey JT. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998 339(11) 713-18. 

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. 

By therapeutic use, or according to similarity in how a drug is used to treat or modify something in the body—For example, with this system amphetamines arc called appetite-suppressant drugs. Note that the reasons some drugs arc used can be much different from their therapeutic effects. When amphetamines arc used non-mcdically, it is often because of their stimulant effects. Similarly, morphine may be used medically as a powerful painkiller, but the street user takes morphine for its euphoric effects. 

Centrally acting appetite suppressant drugs approved for longer term use Sibutramine (Meridia)... 

Physical dependence leading to clear-cut withdrawal symptoms is only rarely seen. Psychological dependence on the drugs currently approved for use in the US, especially when they are taken intermittently (see below), is similarly uncommon (Bray 1993). The great majority of patients who have been prescribed appetite suppressant drugs approved for use in obesity have little or no difficulty in stopping. 

The Value of Appetite Suppressant Drugs in the Treatment of Obesity... 

The majority of appetite-suppressant drugs are congeners of 2-phenethylamine ()3-phen-ethylamine, 37), a compound with close struc-... 

Abenhaim L, Monde Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996 335 609-616. 

Secondary causes of pulmonary arterial hypertension (PAH), including appetite suppressant drugs associated with PAH, have been reviewed [97 j. Newer trends in the treatment of PAH, especially the status of prostacyclin analogues and endothelin-1 receptor antagonists, have been addressed. 

Scheme 32 outlines a high yielding approach to the enantiopure appetite suppressant drug 77. The reduction of the unsaturated aldehyde 74 was reported to occur with modest enantioselectivity in normal fermenting conditions with baker s yeast [155]. When the biotransformation is performed at very low substrate concentration, the e.e. can be raised to more than 90%, suggesting that incomplete enantioselectivity is due to the action of enzymes operating on the same substrate with opposite stereochemical preference [115]. However, an efficient transformation can be performed if the substrate concentration is controlled with the addition of absorbing hydrophobic resins. At 5 g/L 97% recovery and 98% e.e. was obtained. The halohydrin 75 obtained was transformed into the epoxide 76 and finally into the enantiopure 2-/ -benzylmorpholine 77, the more active enantiomer with appetite suppressant activity [26]. 

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