Phentermine

Phentermine
Systematic (IUPAC) name
2-methyl-1-phenylpropan-2-amine
Clinical data
Trade names Adipex-p, Duromine, Metermine, Suprenza
AHFS/Drugs.com monograph
MedlinePlus a682187
Licence data US FDA:link
Pregnancy
category
  • AU: B3
  • US: X (Contraindicated)
Legal status
Dependence
liability		 Low
Addiction
liability		 Very low
Routes of
administration		 Medical: oral,
Recreational: oral, insufflation, intravenous
Pharmacokinetic data
Bioavailability High (almost complete)[1]
Protein binding Approximately 96.3%
Metabolism Hepatic[1]
Biological half-life 25 hours, urinary pH-dependent[1]
Excretion Urinary (62–85% unchanged)[1]
Identifiers
CAS Number 122-09-8 YesY
ATC code A08AA01
PubChem CID 4771
IUPHAR/BPS 7269
DrugBank DB00191 YesY
ChemSpider 4607 YesY
UNII C045TQL4WP YesY
KEGG D05458 YesY
ChEBI CHEBI:8080 YesY
ChEMBL CHEMBL1574 YesY
Synonyms α-methyl-amphetamine
α,α-dimethylphenethylamine
Chemical data
Formula C10H15N
Molar mass 149.233 g/mol
  (verify)

Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant and anorectic drug of the substituted phenethylamine and substituted amphetamine chemical classes, with pharmacology similar to amphetamine. It is used medically as an appetite suppressant.

Phentermine is approved in Australia as an appetite suppressant and is medically prescribed as a diet pill; intended for obese patients and patients that are considered a medical risk due to weight. Phentermine is a prescription that helps aid weight-loss and is designed for short-term use with a combination of exercise and a healthy diet.

In the USA, phentermine is FDA approved, and is currently being studied in combination with other medications for obesity. The first such combination is the appetite suppressant phentermine/topiramate (Qsymia, formerly Qnexa). In 2012, the FDA approved its sale in the United States.

There are various phentermine brands and supplements available through tablets, capsules, and drinks such as: Vites, Adipex and Qsymia (previously known as Qnexa) available in various dosages. Manufacturers of phentermine diet pills have their own 37.5 mg dosages, Phentermine 37.5 mg tablets or capsules are generally manufactured by generic pharmaceutical groups.

Medical uses

Phentermine is used for the short-term treatment of obesity.[2]

Adverse effects

Generally, phentermine appears to be relatively well tolerated.[3]

Adverse effects by incidence[1][4][5][6]

Common (>1% incidence) adverse effects include:

  • Xerostomia (dry mouth)
  • Restlessness
  • Nervousness
  • Euphoria
  • Agitation
  • Arrhythmia
  • Tachycardia
  • Hypertension
  • Diarrhea
  • Vomiting
  • Headache
  • Rash
  • Urinary frequency
  • Facial oedema
  • Unpleasant taste
  • Urticaria
  • Impotence
  • Changes in libido

Contraindications

Phentermine use is contraindicated in those who are:[5][6]

Medicines which may interact with phentermine, such as dexfenfluramine, fenfluramine, furazolidone, or MAOIs (e.g., phenelzine) are contraindicated because of the risk of serious side effects, such as increasing headache, high blood pressure, slow heart rate, elevated temperature, or possibly fatal lung problems, may be increased. Guanadrel (Hylorel) or guanethidine (Ismelin) effectiveness may be decreased by phentermine. Antacids may decrease the excretion of phentermine.[7] Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide) may decrease the excretion of phentermine.[7]

Mechanism of action

Phentermine has some similarity in its pharmacodynamics with its parent compound, amphetamine, as they both are TAAR1 agonists,[8] where the activation of TAAR1 in monoamine neurons facilitates the efflux or, release into the synapse, of these neurochemicals; at clinically relevant doses, phentermine primarily acts as a releasing agent of norepinephrine in neurons, although, to a lesser extent, it releases dopamine and serotonin into synapses as well.[9] Phentermine may also trigger the release of monoamines from VMAT2, which is a common pharmacodynamic effect among substituted amphetamines. The primary mechanism of phentermine's action in treating obesity is the reduction of hunger perception, which is a cognitive process mediated primarily through several nuclei within the hypothalamus (in particular, the lateral hypothalamic nucleus, arcuate nucleus, and ventromedial nucleus). Outside the brain, phentermine releases norepinephrine and epinephrine – also known as noradrenaline and adrenaline respectively – causing fat cells to break down stored fat as well.

History

In 1959, phentermine first received approval from the United States FDA as an appetite-suppressing drug. Phentermine hydrochloride then became available in the early 1970s. It was previously sold as Fastin from King Pharmaceuticals for SmithKline Beecham, but in 1998, it was removed from the market. Medeva Pharmaceuticals sells the name brand of phentermine called Ionamin and Gate Pharmaceuticals sells it as Adipex-P. Phentermine is also currently sold as a generic. Since the drug was approved, almost no clinical studies have been performed.

Phentermine was marketed with fenfluramine as a combination appetite suppressant and fat burning agent under the popular name Fen-Phen. In 1997, after 24 cases of heart valve disease in Fen-Phen users, fenfluramine and dexfenfluramine were voluntarily taken off the market at the request of the FDA.[10] Studies later proved nearly 30% of people taking fenfluramine or dexfenfluramine had abnormal valve findings.

Phentermine is still available by itself in most countries, including the US. However, because it is similar to amphetamine, it is classified as a controlled substance in many countries. Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances.[11] In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act. In contrast, amphetamine preparations are classified as Schedule II controlled substances.

Phentermine is being studied in combination with other medications for obesity. The first such combination is the appetite suppressant phentermine/topiramate (Qsymia formerly Qnexa). In 2012, the FDA approved its sale in the United States.[12]

Trade names

  • Acxion (MX)
  • Adipex P (immediate release)
  • Adiphene (India)
  • Anoxine-AM
  • Ionamin (slow-release resin, Australia, discontinued in the US)
  • Duromine (slow-release resin, New Zealand, Australia and South Africa)
  • Metermine (slow-release resin, Australia)
  • Mirapront
  • Obephen
  • Obermine
  • Obestin-30
  • PhenObestin 37.5
  • Phentermaxx
  • Phentrol
  • Phenterex
  • Phentromin
  • Pro-Fast SA
  • Qsymia (with topiramate)
  • Razin (Israel)
  • Redusa
  • Panbesy
  • Phentermine Trenker
  • Obenix
  • Oby-Trim
  • Teramine
  • Zantryl
  • Sinpet (MX)
  • Supremin (PH)
  • Suprenza (orally disintegrating tablet)
  • Umine (NZ)
  • Weltmine (KP)

Physical and chemical properties

Synthesis

Phentermine can be produced from benzaldehyde and 2-nitropropane as follows:[13][14]

  1. Benzaldehyde and 2-nitropropane are cross-reacted in a variant of the Henry reaction
  2. The nitro group is reduced with hydrogen gas over Raney nickel catalyst
  3. The hydroxyl group is chlorinated with thionyl chloride to yield 2-amino-1-chloro-2-methyl-1-phenylpropane
  4. This is reduced with hydrogen gas over a palladium on magnesium glycinate catalyst to yield the product, phentermine

See also

References

  1. 1 2 3 4 5 "METERMINE (Phentermine)" (PDF). TGA eBusiness Services. iNova Pharmaceuticals (Australia) Pty Limited. 22 July 2013. Retrieved 16 November 2013.
  2. ↑ "phentermine". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  3. ↑ Nelson DL, Gehlert DR (February 2006). "Central nervous system biogenic amine targets for control of appetite and energy expenditure". Endocrine 29 (1): 49–60. doi:10.1385/ENDO:29:1:149. PMID 16622292.
  4. ↑ "ADIPEX-P (phentermine hydrochloride) tablet ADIPEX-P (phentermine hydrochloride) capsule [Teva Select Brands]". DailyMed. Teva Select Brands. April 2013. Retrieved 16 November 2013.
  5. 1 2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  6. 1 2 "phentermine (Rx) - Adipex P, Suprenza". Medscape Reference. WebMD. Retrieved 17 November 2013.
  7. 1 2 "Phentermine". Merck & Co., Inc. 2008. Retrieved 15 May 2008.
  8. ↑ Barak LS, Salahpour A, Zhang X, Masri B, Sotnikova TD, Ramsey AJ, Violin JD, Lefkowitz RJ, Caron MG, Gainetdinov RR (September 2008). "Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor". Mol. Pharmacol. 74 (3): 585–94. doi:10.1124/mol.108.048884. PMC 3766527. PMID 18524885. we confirmed agonistic activity at human TAAR1 of several other compounds, including the trace amines octopamine and tryptamine, the amphetamine derivatives l-amphetamine, d-methamphetamine, (�)-MDMA, and phentermine, and the catecholamine metabolites 3-MT and 4-MT (Bunzow et al., 2001; Lindemann and Hoener, 2005; Reese et al., 2007; Wainscott et al., 2007; Wolinsky et al., 2007; Xie and Miller, 2007; Xie et al., 2007). replacement character in |quote= at position 193 (help)
  9. ↑ Rothman RB, Baumann MH, Dersch CM, et al. (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they dopamine and serotonin". Synapse 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707.
  10. ↑ "FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)". Fda.gov. Retrieved 12 July 2013.
  11. ↑ Convention on Psychotropic Substances (PDF file)
  12. ↑ "FDA approves weight-management drug Qsymia". FDA. 17 July 2012.
  13. ↑ U.S. Patent 2,408,345
  14. ↑ U.S. Patent 2,590,079

External links

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