Investigational Drug Details

Drug ID: D271
Drug Name: Phentermine
Synonyms: alpha,alpha-Dimethylphenethylamine; Phentermine; Phentermine resin
Type: Chemical drug
DrugBank ID: DB00191
DrugBank Description: Phentermine is a sympathomimetic amine anorectic agent and it was introduced in 1959 as part of an anti-obesity combination drug. It is chemically related to amphetamine and it is commonly referred to as an atypical amphetamine. Phentermine has not been reported an addictive potential which allows this agent to be classified under the Schedule IV drugs (low abuse potential). Phentermine was FDA approved for short-term weight management in 1959 and it became widely used in 1960. This initial product, formed by the combination of phentermine with and was discontinued after finding several reports of abnormal valves in nearly 30% of the consumers. Later on, phentermine was approved alone and in combination with topiramate in 2012 as a new alternative that required lower doses of phentermine to obtain the desired effect.
PubChem ID: 4771
CasNo: 122-09-8
Repositioning for NAFLD: Yes
SMILES: C(C(C)(C)N)c1ccccc1
Structure:
InChiKey: DHHVAGZRUROJKS-UHFFFAOYSA-N
Molecular Weight: 149.237
DrugBank Targets: Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; Sodium-dependent dopamine transporter inhibitor; Amine oxidase [flavin-containing] A antagonist; Amine oxidase [flavin-containing] B antagonist; Pro-ne
DrugBank MoA: Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. This increase in noradrenaline concentration in the synaptic cleft results in the stimulation of beta2-adrenergic receptors. Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin. Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger. This combined effect produces a continuous flight-or-fight response in the body which reduces the hunger signal as this state is on the immediate need for energy. Lastly, some reports have indicated that phentermine is a weak inhibitor of monoamine oxidase but this mechanism does not tend to produce a clinically significant response.
DrugBank Pharmacology: It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved. Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure. In clinical studies where phentermine was used as a monotherapy and as combination therapy, this drug has shown an average weight loss of 3.6 kg when compared with the placebo in 2-24 weeks. Patients treated with phentermine also showed increased maintenance of the weight after treatment discontinuation. As well, even though it is a derivative of the amphetamines, it has not been registered to produce any of the effects of amphetamine such as central nervous system stimulation, elevation of blood pressure, tachyphylaxis or QTc prolongation.
DrugBank Indication: 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. Exogenous obesity is considered when the overweight is caused by consuming more food than the person activity level warrants. This condition commonly causes an increase in fat storage. It is an epidemic condition in the United States where over two-thirds of adults are overweight or obese and one in three Americans is obese. In the world, the incidence of obesity has nearly doubled.
Targets: MAOB antagonist; MAOA antagonist; SLC6A2 inhibitor; SLC6A3 inhibitor; SLC6A4 inhibitor; SLC6A2 stimulator; SLC6A3 stimulator
Therapeutic Category: Anorexic; CNS stimulant
Clinical Trial Progress: Phase 4 completed (NCT03849729)
Latest Progress: Under clinical trials

Trial ID Source ID Phases Status Study Results Start Date Last Update Posted
L0775 NCT03849729 Phase 4 Not recruiting No Results Available 02/01/2019 12 December 2020 Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Strategy ID Strategy Synonyms Related Targets Related Drugs
S08 Lifestyle measures Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise -- -- Details
S07 Anti-lipogenesis de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 Details

Article ID PMID Source Title
A08318 32153507 Front Endocrinol (Lausanne) Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review. Details
A12313 30502373 Metabolism Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Details
A27087 19199918 Curr Med Chem Obesity: pathophysiology and clinical management. Details
A43171 32378399 J Obes Metab Syndr Current Long-Term Pharmacotherapies for the Management of Obesity. Details
A50153 35501557 Curr Obes Rep Anti-obesity Medications for the Management of Nonalcoholic Fatty Liver Disease. Details
A50334 35430025 J Clin Lipidol JCL Roundtable. Obesity, Diabetes, and Liver Disease in Relation to Cardiovascular Risk. Details