|Systematic (IUPAC) name|
|Trade names||Adipex-p, Duromine, Metermine, Suprenza|
Recreational: oral, insufflation, intravenous
|Bioavailability||High (almost complete)|
|Protein binding||Approximately 96.3%|
|Half-life||25 hours, urinary pH-dependent|
|Excretion||Urinary (62-85% unchanged)|
|Mol. mass||149.233 g/mol|
|(what is this?)|
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 due to their weight.
Generally, phentermine appears to be relatively well tolerated.
Common (>1% incidence) adverse effects include:
- Xerostomia (dry mouth)
- Urinary frequency
- Facial oedema
- Unpleasant taste
- Changes in libido
Rare (<1% incidence) adverse effects include:
- Valvular heart disease (in combination with dexfenfluramine and fenfluramine; causal relationship unclear)
- Primary pulmonary hypertension
- Increased seizure activity in people with epilepsy
- Withdrawal symptoms on stopping
- Ischaemic events
- Known hypersensitivity or idiosyncratic reaction to sympathomimetic amines
- Taking amphetamine (i.e., Adderall, Dexedrine, Vyvanse), dexfenfluramine, fenfluramine, furazolidone, guanadrel, guanethidine, or have taken a monoamine oxidase inhibitor (MAOI) (e.g., phenelzine) in the last 14 days
- Peptic ulcer
- Prostatic hypertrophy
- Cotreatment with drugs that increase blood pressure
- Contraindicated in cardiac disease (e.g. advanced arteriosclerosis, pulmonary hypertension, uncontrolled hypertension, arrhythmias) and cerebrovascular disease (stroke)
- Pregnant, planning to become pregnant, or are breast-feeding
- Those receiving serotonergic medications such as the selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitor, tricyclic antidepressant, due to the potential for serotonin syndrome to be precipitated by the cotreatment.
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 has some similarity in its pharmacodynamics with its parent compound, amphetamine, as they both are TAAR1 agonists. 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.
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.
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. 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. 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.
||This section provides insufficient context for those unfamiliar with the subject. (November 2014)|
- 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.
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