|Systematic (IUPAC) name|
|Pregnancy cat.||C (US)|
|Legal status||Schedule IV (US)|
|Routes||Oral, Insufflation, Intravenous|
|Bioavailability||Peak plasma levels occur within 1 to 4.5 hours. Absorption is usually complete by 4 to 6 hours|
|Protein binding||Approximately 96.3%|
|Half-life||16 to 31 hours|
|Mol. mass||149.233 g/mol|
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Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, with pharmacology similar to amphetamine. It is used medically as an appetite suppressant.
It is approved as an appetite suppressant to help reduce weight in obese patients when used short-term and combined with exercise, diet, and behavioral modification. It is typically prescribed for individuals who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.
Phentermine is used for the short-term treatment of obesity.
Generally, phentermine appears to be relatively well tolerated. It can produce side effects consistent with its catecholamine-releasing properties, e.g., tachycardia (increased heart rate) and elevated blood pressure, but the incidence and magnitude of these appear to be less than with the amphetamines. Because phentermine acts through sympathomimetic pathways, the drug may increase blood pressure and heart rate. It may also cause palpitations, restlessness, and insomnia. Additionally, phentermine has the potential to cause psychological dependence. After short-term use, tolerance begins and can be followed by rebound weight gain.
Cardiovascular side effects include palpitations, tachycardia, and elevation of blood pressure. In the central nervous system, it can cause overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, and headache. Its gastrointestinal effects include dryness of the mouth, unpleasant taste, diarrhea, constipation, and other gastrointestinal disturbances. It may also cause allergic effects - urticaria and changes in libido.
Its less common, but more severe, side effects include:
- Convulsions (seizures)
- Hostility with urge to attack
- Bizarre behavior
- Mental or mood changes
- Exaggerated sense of well-being
- Irregular blood pressure
- Severe or persistent light-headedness, fainting or headache
- Periods of mania followed by period of depression
- Fast or irregular heartbeat
- Overactive reflexes
- Tremors, trembling or shaking
- Severe nausea, vomiting or diarrhea
- Stomach cramps
- Primary pulmonary hypertension
- Regurgitant cardiac valvular disease
- Pounding in the chest or shortness of breath
Phentermine use is contraindicated in those who are:
- Allergic to phentermine, any of its metabolites or other sympathomimetics (e.g., pseudoephedrine)
- Taking amphetamine (i.e., Adderall, Dexedrine, Vyvanse), bupropion (WellButrin), dexfenfluramine, fenfluramine, furazolidone, guanadrel, guanethidine, or have taken a monoamine oxidase inhibitor (MAOI) (e.g., phenelzine) in the last 14 days
- Subject to severe high blood pressure, an overactive thyroid, glaucoma, heart or blood vessel disease, severe narrowing of the blood vessels, diabetes, a brain or spinal cord disorder, hardening of the arteries, or high cholesterol or lipid levels
- In an agitated state, or have a history of substance abuse
- Pregnant, planning to become pregnant, or are breast-feeding
- Taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
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. Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide) may decrease the excretion of phentermine.
Mechanism of action
Phentermine works on the hypothalamus portion of the brain to stimulate the adrenal glands to release norepinephrine, a neurotransmitter or chemical messenger that signals a fight-or-flight response, reducing hunger. Phentermine works outside the brain, as well, to release epinephrine or adrenaline, causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction. At clinically relevant doses, phentermine also releases serotonin and dopamine, but to a much lesser extent than that of norepinephrine.
Dosing and administration
Generally, it is recommended by the U.S. Food and Drug Administration (FDA) that phentermine should be used short-term (usually interpreted as 'up to 12 weeks'), while following nonpharmacological approaches to weight loss such as healthy dieting and exercise.
In 1959, phentermine first received approval from the 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.
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. 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 amphetamines, it is classified as a controlled substance in many countries. Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances. 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. One such combination is the appetite suppressant phentermine/topiramate (Qsymia or Qnexa). In 2012, the FDA approved its sale in the United States.
- Benzaldehyde and 2-nitropropane are cross-reacted in a variant of the Henry reaction
- The nitro group is reduced with hydrogen gas over Raney nickel catalyst.
- The hydroxyl group is chlorinated with thionyl chloride to yield 2-amino-1-chloro-2-methyl-1-phenylpropane.
- This is reduced with hydrogen gas over a palladium on magnesium glycinate catalyst to yield the product, phentermine.
- "phentermine". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
- 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.
- "Phentermine". Merck & Co., Inc. 2008. Retrieved 2008-05-15. Unknown parameter "unused_data=" ignored
- 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.
- "HEALTH ADVISORY ON FENFLURAMINE/PHENTERMINE FOR OBESITY". Archived from the original on 30 May 2009. Retrieved 30 May 2009.
- Incb.org (PDF file)
- "FDA approves weight-management drug Qsymia". FDA. July 17, 2012.
- U.S. Patent 2,408,345
- U.S. Patent 2,590,079
- MedLine Plus - Phentermine
- International Programme on Chemical Safety - Phentermine
- U.S. National Library of Medicine: Drug Information Portal - Phentermine
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