Appetite Suppressants for Obesity Treatment

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Appetite regulation can be mediated by a number of factors. Among the many factors a research review notes that hormones, neuropeptides, monoamine transmitters, serotonin, dopamine (DA), and norepinephrine (NE) to be important mediators (Rothman & Baumann, 2000). Of these factors, transmitter molecules that act in the brain are the most implicated factors that explain the mechanism through which phentermine leads to appetite suppression.

How Phentermine Generates Appetite Suppressing Effect


With its chemical and structural association to amphetamines, a group of compounds with psychomotor stimulant activity, phentermine (PHE) also works through CNS-stimulant activity. According to the research review, PHE is inhibits NE (re-) uptake while promoting its release. Further, PHE promotes secretion of neuronal (nerve cells) DA and serotonin (5-HT). The availability of these transmitter substances and especially serotonin, a biogenic amine, in the brain controls effects such as satiety, consciousness and stress relief.

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Drugs, however, do not mediate the release of these substances directly but rather through their interaction with receptors. By the presence of appropriate ligand binding sites, receptors provide areas onto which biochemical agents such as drugs attach. The products of drug biotransformation (metabolites) bind to their corresponding receptor site resulting into changes in the receptor-protein conformation. Being members of cellular membranes such as those that enclose transmitters, the conformational changes can either block the channels of transmission (inhibit uptake from synapses) or open these channels (ensure release into synapses) thus availing the neurotransmitter substance required to convey hormonal regulation signals in the synapses.

Other Weight-Reducing Drugs and Side Effects of Phentermine


Some treatment alternatives to phentermine that work in a similar fashion are a combination of phentermine and fenfluramine [FEN] (Phen-Fen) and sibutramine. Other drugs in this group that were once used for obesity treatment such as pure FEN and its more potent structural analogue (d)-fenfluramine (dFEN) are no longer used in humans due to their adverse effects. Drugs such as orlistat (trade name) that work by inhibiting enzymes involved in fat digestion hence blocking food absorption are also possible therapies for overweight.

Some of the adverse effects of phentermine use are directly associated to its working mechanism. A study comparing efficacy of PHE and Phen-Fen for instance noted adverse effects such as dry mouth, insomnia, and constipation in some of the participants (Li, et al. 2003). The increased risk of more serious adverse effects such as primary pulmonary hypertension (PPH) with use of these drugs, as advanced in the research review, however necessitates the development of better therapies for treating obesity.

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