Anorexigens

Appetite-suppressing. Neuropqrtide modulators and gut hormones with anorexigenic effects are a-melanocortin-stimulating hormone (a-MSH), cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1), leptin, insulin, oxyntomodulin, pancreatic peptide PP, peptide YY and PYY3 36, and others. 

CART (cocaine- and amphetamine-regulated transcript) is a hypothalamic peptide that inhibits both normal and starvation-induced feeding when injected into cerebral ventricles of rats. CART is co-localized with the anorexigenic peptide a-melanocyte-stimulating hormone in neurons of the arcuate nucleus. Secretion of CART is stimulated by leptin and CART may be an endogenous inhibitor of food intake. 

Central nervous system Reduction of body weight Reduced appetite changed expression of anorexigenic (e.g., POMC) and orexigenic (e.g., NPY) hypothalamic neuropeptides... 

Bever, K, Perry, P. Dexfenfluramine hydrochloride an anorexigenic agent. Am. J. Health Syst. Pharm. 54 2059, 1976. 

Perhaps, the most significant success of receptorome screening was the implication of the serotonin 5-HT2B receptor in the VHD associated with fenfluramine use. The anorexigen fenfluramine was widely used in the 1990s as an adjunct to diet and exercise, with great success [8]. Originally, racemic fenfluramine was used with... 

Yu G, Maskray V, Jackson SH, Swift CG, Tiplady B. (1991). A comparison of the central nervous system effects of caffeine and theophylline in elderly subjects. BrJ Clin Pharmacol. 32(3) 341-45. Zelger JL, Carlini EA. (1980). Anorexigenic effects of two amines obtained from Catha edulis Forsk. (Khat) in rats. Pharmacol Biochem Behav. 12(5) 701-5. 

Diabetes Insulin requirements in diabetes mellitus may be altered in association with the use of anorexigenic drugs and the concomitant dietary restrictions. 

Fenfluramine (Pondimin) and phentermine (Adipex-P, Fastin) are anorexigenic drugs that produce depression of the CNS and at one time were used (Fen-phen) in the treatment of obesity. Sibutramine (Meridia) is also available for the treatment of obesity. 

Together with GFIB and ecstasy, amphetamines are often referred to as "club drugs," because they are increasingly popular in the club scene. They are often produced in small clandestine laboratories, which makes their precise chemical identification difficult. They differ from ecstasy chiefly in the context of use intravenous administration and "hard core" addiction is far more common with amphetamines, especially methamphetamine. In general, amphetamines lead to elevated catecholamine levels that increase arousal and reduce sleep, whereas the effects on the dopamine system mediate euphoria but may also cause abnormal movements and precipitate psychotic episodes. Effects on serotonin transmission may play a role in the hallucinogenic and anorexigenic functions as well as in the hyperthermia often caused by amphetamines. 

Leptin Stimulates Production of Anorexigenic Peptide Hormones... 

The anorexigenic (appetite-suppressing) neurons in the arcuate nucleus produce a-melanocyte-stimulating hormone (a-MSH), formed from its polypeptide precursor pro-opiomelanocortin (POMC Fig. 23-6). Release of a-MSH causes the next neuron in the circuit to send the signal to the brain, Stop eating ... 

As noted in the text, serotonin appears to be related to several general behaviors such as sleep, emotion, sex, and appetite, and early studies with the amine suggested that it could reduce food intake in animals, an anorexigenic effect. 

Fenfluramine, a racemic chemical more closely related to amphetamine than to serotonin, affects brain levels of serotonin and its metabolites at relatively low doses. It was introduced as an anorexigenic drug almost 20 years ago. Its d- isomer, J-fenfluramine (dexfenfluramine, Redux) was about twice as potent as fenfluramine. After several controlled clinical trials demonstrated that dexfenfluramine could help patients maintain weight loss for at least a year, it was quickly introduced into the market in the USA and became a best-selling drug overnight. 

These findings precipitated the widespread use of a fenfluramine-phentermine combination therapy that came to be known as Fen-Phen. The combined use of the two anorexigens had never been approved by the FDA, nor had the longterm safety of the therapy ever been established. Nevertheless, weight loss clinics specializing in Fen-Phen therapy were established throughout the country. In 1996, the FDA narrowly approved the more potent, less adverse-effect-prone (+)stereoisomer of fenfluramine, dexfenfluramine, for less-than-l-yr use in the treatment of obesity. The New York Times reported that in 1996, 18 million prescriptions had been written for fenfluramine alone or in combination with phentermine and that about 6 million Americans took the drug (37). 

Setola V, Dukat M, Glennon RA, Roth BL. Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor. Mol Pharmacol 2005 68(l) 20-33. 

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