General
Preferred name
PHENTERMINE
Synonyms
PHENTERMINE HYDROCHLORIDE ()
Phentermine HCl ()
Phentermine hydrochloride civ ()
NSC-44090 ()
Adipex-P ()
Ona-Mast ()
Fastin ()
Lomaira ()
TORA ()
Obestin-30 ()
WILPO ()
Suprenza ()
Zantryl ()
Oby-Trim ()
Phentermine resin complex ()
Phentermine resin ()
Ionamin ()
Duromine ()
NSC-759163 ()
Qsiva ()
Phentermine Resin 30 ()
Phentermine (hydrochloride) ()
P&D ID
PD010178
CAS
35373-71-8
122-09-8
1197-21-3
Tags
natural product
drug
available
Approved by
FDA
First approval
1959
1973
Drug Status
illicit
approved
Drug indication
Obesity
Appetite Suppressant (systemic)
Anorexic,Appetite Suppressant (systemic)
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
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.[A174370] Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.[A174367] 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.[A174367] 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.[A174370]
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.[A174367] Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin.[L5233] Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger.[T403] 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.[T403] 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.[T49]
ROE
Phentermine is excreted mainly in the urine from which about 70-80% of the administered dose can be found as the unchanged drug.[A174370]
HALF-LIFE
The mean terminal half-life of phentermine is reported to be of approximately 20 hours.[A174370] In conditions where there is acidic urine (pH <5), the elimination half-life is of 7-8 hours.[T49]
TOXICITY
The reported LD50 after oral administration of phentermine in rats is reported to be of 151 mg/kg.[L5239] Reports of acute overdose include restlessness, tremors, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations and panic state followed by fatigue, and depression. In the cardiovascular system, there are reports of tachycardia, arrhythmia, hypertension, hypotension, circulatory collapse. In the GI tract, there are symptoms of nausea, vomiting, diarrhea and abdominal cramps. The management of acute overdosage includes symptomatic treatment as well as lavage and sedation with barbiturates.[FDA label] On the other hand, chronic overdosage is marked by dermatoses, insomnia, irritability, hyperactivity and personality changes. In severe cases, it can derive into a schizophrenia-like psychosis.[FDA label] Studies regarding the carcinogenic potential have not been performed. On the case of mutagenic assays, phentermine was shown to not be mutagenic nor clastogenic.[FDA label]
ABSORPTION
Phentermine shows a dose-dependent pharmacokinetic profile. After oral administration of a dose of 15 mg, the maximal concentration was achieved after 6 hours and its bioavailability was not affected by the consumption of high-fat meals.[A174370] The reported plasma concentration at steady-state is of around 200 ng/ml as observed in clinical trials.[T49]
METABOLISM
Phentermine undergoes minimal p-hydroxylation, N-oxidation and N-hydroxylation followed by conjugation. The total proportion of the drug that goes under metabolism only represents about 6% of the administered dose where about 5% is represented by the N-oxidized and N-Hydroxylated metabolites.[T49]
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.[A174367] Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin.[L5233] Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger.[T403] 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.[T403]; ; 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.[T49]
DESCRIPTION
Phentermine is a stimulant similar to amphetamines.
(GtoPdb)
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.[FDA label] 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.[A174391]
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.[FDA label]; ; 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.[A174391]
PHARMACODYNAMICS
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.[A174370] Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.[A174367]; ; 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.[A174367] 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.[A174370]
TOXICITY
The reported LD50 after oral administration of phentermine in rats is reported to be of 151 mg/kg.[L5239] Reports of acute overdose include restlessness, tremors, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations and panic state followed by fatigue, and depression. In the cardiovascular system, there are reports of tachycardia, arrhythmia, hypertension, hypotension, circulatory collapse. In the GI tract, there are symptoms of nausea, vomiting, diarrhea and abdominal cramps. The management of acute overdosage includes symptomatic treatment as well as lavage and sedation with barbiturates.[FDA label]; ; On the other hand, chronic overdosage is marked by dermatoses, insomnia, irritability, hyperactivity and personality changes. In severe cases, it can derive into a schizophrenia-like psychosis.[FDA label]; ; Studies regarding the carcinogenic potential have not been performed. On the case of mutagenic assays, phentermine was shown to not be mutagenic nor clastogenic.[FDA label]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
15
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
Ki Database
NCATS Inxight Approved Drugs
Prestwick Chemical Library
ReFrame library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
60
Molecular Weight
149.12
Hydrogen Bond Acceptors
1
Hydrogen Bond Donors
1
Rotatable Bonds
2
Ring Count
1
Aromatic Ring Count
1
cLogP
1.97
TPSA
26.02
Fraction CSP3
0.4
Chiral centers
0.0
Largest ring
6.0
QED
0.68
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Class
Appetite Depressants
Source data
