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MolPort-002-043-208
Also known as: 122-09-8, 2-methyl-1-phenylpropan-2-amine, Duromine, Ionamin, 1,1-dimethyl-2-phenylethylamine, Alpha,alpha-dimethylphenethylamine
Molecular Formula
C10H15N
Molecular Weight
149.23  g/mol
InChI Key
DHHVAGZRUROJKS-UHFFFAOYSA-N
FDA UNII
C045TQL4WP

A central nervous system stimulant and sympathomimetic with actions and uses similar to those of DEXTROAMPHETAMINE. It has been used most frequently in the treatment of obesity.
Phentermine is a Sympathomimetic Amine Anorectic. The physiologic effect of phentermine is by means of Appetite Suppression, and Increased Sympathetic Activity.
1 2D Structure

MolPort-002-043-208

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-methyl-1-phenylpropan-2-amine
2.1.2 InChI
InChI=1S/C10H15N/c1-10(2,11)8-9-6-4-3-5-7-9/h3-7H,8,11H2,1-2H3
2.1.3 InChI Key
DHHVAGZRUROJKS-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC(C)(CC1=CC=CC=C1)N
2.2 Other Identifiers
2.2.1 UNII
C045TQL4WP
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Adipex P

2. Adipex-p

3. Adipexp

4. Duromine

5. Hydrochloride, Phentermine

6. Ionamine

7. Phentermine Hydrochloride

2.3.2 Depositor-Supplied Synonyms

1. 122-09-8

2. 2-methyl-1-phenylpropan-2-amine

3. Duromine

4. Ionamin

5. 1,1-dimethyl-2-phenylethylamine

6. Alpha,alpha-dimethylphenethylamine

7. Phenterminum

8. Fentermina

9. Mirapront

10. Lipopill

11. Adipex-p

12. 2-phenyl-tert-butylamine

13. Qsiva

14. Benzeneethanamine, Alpha,alpha-dimethyl-

15. Phentermine Resin

16. Normephentermine

17. Benzeneethanamine, .alpha.,.alpha.-dimethyl-

18. Lonamin

19. Omnibex

20. Linyl

21. .alpha.,.alpha.-dimethylphenethylamine

22. Nsc-759163

23. C045tql4wp

24. Chembl1574

25. Chebi:8080

26. Obermine

27. Phentrol

28. Phentrol 2

29. Phentrol 3

30. Phentrol 4

31. Dea No. 1640

32. 1,1-dimethyl-2-phenyl-ethylamine

33. Phenyl-tert-butylamine

34. Alpha-benzylisopropylamine

35. Phenyl-tertiary-butylamine

36. Fentermina [inn-spanish]

37. Phenterminum [inn-latin]

38. Phentermine [usan:inn:ban]

39. Phentermine Resin Complex

40. 2-amino-2-methyl-1-phenylpropane

41. Rcra Waste Number P046

42. Alpha,alpha-dimethylbenzeneethanamine

43. Alpha,alpha-dimethyl-beta-phenylethylamine

44. Hsdb 3158

45. Sr-05000001805

46. (alpha,alpha)-dimethylphenethylamine

47. Einecs 204-522-1

48. Ethanamine, 1,1-dimethyl-2-phenyl-

49. Phentermine (usan/inn)

50. Rcra Waste No. P046

51. Unii-c045tql4wp

52. Brn 0970319

53. Phenethylamine, Alpha,alpha-dimethyl-

54. Alpha,alpha-dimethylphenethylamine Solution

55. Phentermine [mi]

56. Phentermine [inn]

57. 1-benzyl-iso-propyl Amine

58. Phentermine [hsdb]

59. Phentermine [usan]

60. Ec 204-522-1

61. Phentermine [vandf]

62. Phentermine [mart.]

63. Schembl26615

64. Phentermine [who-dd]

65. Gtpl7269

66. 122-09-8 (free Base)

67. Dtxsid9023461

68. Hms2093b16

69. Pharmakon1600-01505660

70. Qsymia Component Phentermine

71. Phentermine 0.1 Mg/ml In Methanol

72. Phentermine 1.0 Mg/ml In Methanol

73. Zinc8403947

74. .alpha..alpha.dimethylphenethylamine

75. Bdbm50246598

76. Nsc759163

77. Akos004123261

78. Phentermine Component Of Qsymia

79. Ab02355

80. Db00191

81. Nsc 759163

82. Ncgc00263911-02

83. Phenethylamine, .alpha.,.alpha.-dimethyl-

84. Sbi-0206817.p001

85. D1291

86. Ft-0716831

87. C07438

88. D05458

89. Q418157

90. Sr-05000001805-1

91. Sr-05000001805-2

92. Brd-k96319534-001-01-7

93. Phentermine Solution, 1.0 Mg/ml In Methanol, Ampule Of 1 Ml, Certified Reference Material

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 149.23 g/mol
Molecular Formula C10H15N
XLogP31.9
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count1
Rotatable Bond Count2
Exact Mass149.120449483 g/mol
Monoisotopic Mass149.120449483 g/mol
Topological Polar Surface Area26 Ų
Heavy Atom Count11
Formal Charge0
Complexity112
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 6  
Drug NameAdipex-p
PubMed HealthPhentermine (By mouth)
Drug ClassesAppetite Suppressant, Centrally Acting
Drug LabelPhentermine hydrochloride USP has the chemical name of ,,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:C10H15N HCl M.W. 185.7Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder which i...
Active IngredientPhentermine hydrochloride
Dosage FormTablet; Capsule
RouteOral
Strength37.5mg
Market StatusPrescription
CompanyTeva

2 of 6  
Drug NamePhentermine resin complex
Drug LabelSuprenza is an orally disintegrating tablet (ODT) of phentermine hydrochloride, USP. Phentermine hydrochloride is a sympathomimetic amine anorectic. Its chemical name is ,,-dimethylphenethylamine hydrochloride. The structural formula is as follow...
Active IngredientPhentermine resin complex
Dosage FormCapsule, extended release
RouteOral
Strengtheq 15mg base; eq 30mg base
Market StatusPrescription
CompanyLannett Holdings

3 of 6  
Drug NameSuprenza
Active IngredientPhentermine hydrochloride
Dosage FormTablet, orally disintegrating
RouteOral
Strength37.5mg; 30mg; 15mg
Market StatusPrescription
CompanyCitius Pharms

4 of 6  
Drug NameAdipex-p
PubMed HealthPhentermine (By mouth)
Drug ClassesAppetite Suppressant, Centrally Acting
Drug LabelPhentermine hydrochloride USP has the chemical name of ,,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:C10H15N HCl M.W. 185.7Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder which i...
Active IngredientPhentermine hydrochloride
Dosage FormTablet; Capsule
RouteOral
Strength37.5mg
Market StatusPrescription
CompanyTeva

5 of 6  
Drug NamePhentermine resin complex
Drug LabelSuprenza is an orally disintegrating tablet (ODT) of phentermine hydrochloride, USP. Phentermine hydrochloride is a sympathomimetic amine anorectic. Its chemical name is ,,-dimethylphenethylamine hydrochloride. The structural formula is as follow...
Active IngredientPhentermine resin complex
Dosage FormCapsule, extended release
RouteOral
Strengtheq 15mg base; eq 30mg base
Market StatusPrescription
CompanyLannett Holdings

6 of 6  
Drug NameSuprenza
Active IngredientPhentermine hydrochloride
Dosage FormTablet, orally disintegrating
RouteOral
Strength37.5mg; 30mg; 15mg
Market StatusPrescription
CompanyCitius Pharms

4.2 Therapeutic Uses

Adrenergic Agents; Adrenergic Uptake Inhibitors; Appetite Depressants; Central Nervous System Stimulants; Dopamine Agents; Dopamine Uptake Inhibitors

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


... Phentermine /is/ indicated in the short-term (a few weeks) treatment of exogenous obesity in conjunction with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of > or = 30 kg of body weight per height in meters squared (kg/sq m) or in patients with a body mass index of > or = 27 kg/sq m in the presence of risk factors such as hypertensin, diabetes, or hyperlipidemia. /Included in US product labeling /

Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 438


Anorexic

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1304


... /Phentermine hydrochloride & phentermine resin/ were developed in hope that they would produce greater anorexiant effect with fewer untoward reactions than amphetamines. In spite of minor differences in their actions & untoward effects ... /neither/ has been found to be more effective than dextroamphetamine. /Phentermine hydrochloride and Phentermine resin/

American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 487


4.3 Drug Warning

Pulmonary hypertension has been reported in patients receiving phentermine in combination with dexfenfluramine (no longer commercially available in the US), fenfluramine (no longer commercially available in the US), and in those with a history of receiving at least one other anorexigenic agent; however, the possibility of an association between pulmonary hypertension and the use of phentermine as monotherapy cannot be ruled out. Primary pulmonary hypertension is a rare, frequently fatal pulmonary disease. The initial symptom of pulmonary hypertension generally is dyspnea. Other initial manifestations include angina pectoris, syncope, or edema of the lower extremities. Phentermine should be discontinued in any patient who develops new, unexplained symptoms of dyspnea, angina, syncope, or edema of the lower extremities. Such patients should be evaluated for the possible presence of pulmonary hypertension. In addition, patients receiving phentermine should be advised to report immediately any deterioration in exercise tolerance

McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2384


Valvular Heart Disease: Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricuspid valves, has been reported in otherwise healthy persons who had taken a combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.

Physicians Desk Reference. 59th ed. Thomson PDR. Montvale, NJ 2005., p. 1324


Phentermine should not be used in combination with selective serotonin-reuptake inhibitor antidepressants /SSRI/ (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) or MAO inhibitors, since severe adverse reactions may occur. In addition, one manufacturer of phendimetrazine tartrate (Plegine) states that phendimetrazine should not be used in combination with other anorexigenic agents (e.g., phentermine) since valvulopathy and primary pulmonary hypertension have been reported in patients receiving phendimetrazine who had received at least one other anorexigenic agent.

McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2384


Habituation or addiction has been reported with similar drugs and the possibility of its occurrence should be considered with phentermine.

McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2384


For more Drug Warnings (Complete) data for PHENTERMINE (15 total), please visit the HSDB record page.


4.4 Drug 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.


FDA Label


5 Pharmacology and Biochemistry
5.1 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.


5.2 MeSH Pharmacological Classification

Appetite Depressants

Agents that are used to suppress appetite. (See all compounds classified as Appetite Depressants.)


Adrenergic Agents

Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. (See all compounds classified as Adrenergic Agents.)


Sympathomimetics

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)


Central Nervous System Stimulants

A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. (See all compounds classified as Central Nervous System Stimulants.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
PHENTERMINE
5.3.2 FDA UNII
C045TQL4WP
5.3.3 Pharmacological Classes
Established Pharmacologic Class [EPC] - Sympathomimetic Amine Anorectic
5.4 ATC Code

A - Alimentary tract and metabolism

A08 - Antiobesity preparations, excl. diet products

A08A - Antiobesity preparations, excl. diet products

A08AA - Centrally acting antiobesity products

A08AA01 - Phentermine


5.5 Absorption, Distribution and Excretion

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. The reported plasma concentration at steady-state is of around 200 ng/ml as observed in clinical trials.


Route of Elimination

Phentermine is excreted mainly in the urine from which about 70-80% of the administered dose can be found as the unchanged drug.


Volume of Distribution

The reported volume of distribution for phentermine is reported to be of 5 L/kg.


Clearance

The reported clearance when administered orally is 8.79 L/h as observed in pharmacokinetic population studies.


Absorbed readily after oral administration. Distributed widely throughout body.

Cowl, C.T. Physician's Handbook 10th edition. Lippincott Williams & Wilkins, Philadelphia, PA. 2003, p. 973


The volume of distribution is 3 to 4 L/kg ... A majority of the drug is excreted unchanged in the urine. An average of 48% of the dose is excreted in the urine in 24 hours, which increases to 84% in acidic urine.

Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 877


Elimination is primarily renal; excretion is increased by acidifying the urine.

Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 438


N-hydroxyphentermine is rapidly reduced back to phentermine. This pathway recycles parent drug, which then has a longer duration of action.

Jenden DJ et al; In Central Mechanisms Of Anorectic Drugs; Garattini S, Samanin R, eds, p. 165-77 (1978)


5.6 Metabolism/Metabolites

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.


Phentermine is not significantly biotransformed; 70 to 80 % of a given dose is excreted unchanged in the urine.

Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 438


There are two primary pathways of oxidative metabolism: n-hydroxylation to n-hydroxyphentermine & p-hydroxylation to para-hydroxyphentermine. N-hydroxyphentermine is metabolized further to alpha-nitrophentermine. In rats the dominant pathway is p-hydroxylation to give para-hydroxyphentermine, accounting for more than 60% of administered dose. P-hydroxylation reactions in rat liver microsomes indicated that phentermine metabolism was inhibited by skf525a & iprindol, and was not inducible with phenobarbital or 3-methylcholanthrene, suggesting a system different from aromatic c-hydroxylation. The n-hydroxylation reaction for rabbit & guinea pig (two-enzyme system) & rat (single enzyme system) is the reduced form of nicotinamide-adenine dinucleotide phosphate-dependent, inhibited by carbon monoxide & induced by phenobarbital, suggesting involvement of cytochrome p450 system.

Jenden DJ et al; In Central Mechanisms Of Anorectic Drugs; Garattini S, Samanin R, eds, p. 165-77 (1978)


Although no quantitative data are available, urinary metabolites found in man are p-hydroxyphentermine and n-hydroxyphentermine. N-hydroxy metabolite can be reduced in vivo but conversion to this metabolite appears to be inefficient means of elimination.

Jenden DJ et al; In Central Mechanisms Of Anorectic Drugs; Garattini S, Samanin R, eds, p. 165-77 (1978)


The role of the cytochrome p450 system in the oxidation of phentermine to N-hydroxyphentermine by liver microsomal prepn was studied in a reconstituted system which consisted of cytochrome p450 and the reduced form of nicotinamide-adenine dinucleotide phosphate cytochrome p450 reductase purified from liver microsomes of phenobarbital-induced rabbits. In this system, phentermine was oxidized to N-hydroxyphentermine. The reaction was the reduced form of nicotinamide-adenine dinucleotide phosphate-dependent and required the presence of both the cytochrome p450 and reductase preparations.

PMID:6815477 Duncan JD, Cho AK; Mol Pharmacol 22 (2): 235-36 (1982)


5.7 Biological Half-Life

The mean terminal half-life of phentermine is reported to be of approximately 20 hours. In conditions where there is acidic urine (pH <5), the elimination half-life is of 7-8 hours.


... Elimination half-life is approximately 7-8 hours in acid urine (pH5), compared with 19-24 hours under normal conditions.

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 631


S(+)-phentermine was eliminated much more rapidly in rat (k= 1.32/hr) after iv administration than in man (k= 0.029/hr) after oral dose. Half-lives were 25-35 min in rat & 12-24 hr in man.

Jenden DJ et al; In Central Mechanisms Of Anorectic Drugs; Garattini S, Samanin R, eds, p. 165-77 (1978)


5.8 Mechanism of Action

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.


Although the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications ... are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite. ... It has not been established that the actions of these medications in treating obesity is primarily suppression of appetite; other CNS actions and/or metabolic effects, such as decreased gastric acid secretion or increased energy expenditure, may be involved.

Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 439


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