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Pathway Description
Phentermine Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2022-03-10
Last Updated: 2023-10-25
Phentermine is an oral sympathomimetic anorectic drug used as a short-term adjunct therapy that is included in a regimen of weight reduction in cases of exogenous obesity.
Phentermine is indicated, alone or in combination with topiramate, as a short-term adjunct, not pass a few weeks, in a regimen of weight reduction based on exercise, behavioral modifications and caloric restriction in the management of exogenous obesity for patients with an initial body mass index (BMI) greater than 30 kg/m2 or greater than 27 kg/m2 in presence of other risk factors such as controller hypertension, diabetes or hyperlipidemia.
Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. Phentermine enters the neuron through the norepinephrine reuptake transporter (NET) and in transported into synaptic vesicles through vesicular monoamine transporter 2 (VMAT2). In these synaptic vesicles, phentermine displaces the norepinephrine stored, and stimulates VMAT2 to spew out the stored norepinephrine into the cytosol. Phentermine is also an agonist for the trace amine-associated receptor-1 (TAAR1), which when activated, causes the reversal of NET, leading to norepinephrine in the cytosol being transported out into the synapse. Phentermine is also a weak inhibitor of monoamine oxidase, an enzyme responsible for metabolizing catecholamines like norepinephrine. The overall effect of phentermine is to increase synaptic concentration of norepinephrine and inhibit its reuptake and metabolism.
The norepinephrine in the synapse activates beta-2 and alpha-1 adrenergic receptors on post-synaptic neurons. Activation of these receptors ultimately leading to the feeling of satiety/ decreased hunger perception and therefore, decreased food intake. Phentermine may also cause the release of norepinephrine in the periphery. Postganglionic sympathetic neurons release noradrenalin in target organs. Via this route, lipolysis in adipose tissue is stimulated mainly via activation of β3-adrenoceptors, which are selectively expressed on adipocytes.
Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger.
Side effects of taking phentermine include nervousness, excitability, insomnia, headache, dry mouth, sweating, tachycardia, palpitations, nausea, constipation, and thirst. Rare severe adverse events include atrial fibrillation, acute psychosis and pulmonary hypertension.
References
Phentermine Pathway References
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Phentermine
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Pubmed: 14702039
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