Antiobesity Drugs

Abstract

AbstractObesity is a difficult condition to treat. Appetite suppressants have been widely used as an adjunct to dietary restriction and sympathomimetic amines have traditionally been used for this purpose. These agents have not proven particularly useful and frequently cause unacceptable side effects; hence their popularity has been waning. The most promising newer drugs work through a serotoninergic mechanism and hold considerable promise at least for certain obese patients. The majority of formerly obese patients eventually regain excess weight lost and thus a truly successful program must include behavior modification. In the central nervous system, sympathetic nervous stimulation results in increases in wakefulness, psychomotor activity, and reduction of appetite. Compounds structurally related to the endogenous sympathomimetic amines norepinephrine and epinephrine have classically been employed as appetite suppressants. These compounds act primarily by indirect mechanism involving displacement of norepinephrine from presynaptic nerve storage vesicles rather than by a direct effect at the receptor level. Whereas they vary in degree, all of them share similar liabilities of cardiovascular side effects, the potential for central nervous system (CNS) stimulation, the development of tolerance, and abuse potential. All, with the exception of mazindol, are derivatives of phenethylamine. Following the Federal Controlled Drug Act of 1970, compounds available in the United States were classified into one of five schedules according to medical utility and abuse potential. They include Schedule II, eg, amphetamine sulfate (C9H14SO4N, Benzedrine) and dextroamphetamine sulfate (C9H14NO4S, Dexedrine); Schedule III, eg, phendimetrazine tartrate (C16H23NO7, Plegine); and Schedule IV, eg, phenteramine hydrochloride (C10H16NCl, Fastin, Adipex‐P, Ionamin). Only drugs in Schedules III and IV are commonly employed for obesity and of them, phenylpropanolamine is available over the counter. Serotoninergic neurons utilize serotonin, C10H12N2O, which is 5‐hydroxytryptamine (5‐HT), as a neurotransmitter. Central serotoninergic neurons play an important role in determining mood and food intake. Fluoxetine (C17H19ClF3NO, Prozac) is a serotonin reuptake inhibitor, is marketed by Eli Lilly as an antidepressant. It was observed in animal studies that fluoxetine decreased meal size and promoted weight loss, and these findings have been extended to humans in clinical trials. Other drugs include gut hormones, lipid adsorption inhibitors, and thermogenic agents.