Article: Phentermine

Phentermine
Systematic (IUPAC) name
2-methyl-1-phenyl-propan-2-amine
Identifiers
CAS number	122-09-8
ATC code	A08AA01 C01CA11
PubChem	4771
DrugBank	APRD00093
Chemical data
Formula	C10H15N
Mol. weight	149.233 g/mol
Pharmacokinetic data
Bioavailability	Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours
Protein binding	Approximately 96.3%
Metabolism	hepatic
Half life	16 to 31 hours
Excretion	Urinary elimination
Therapeutic considerations
Pregnancy cat.	C(United States); ? (Australia)
Legal status	C-IV (US)
Routes	Oral

Phentermine is a phenethylamine primarily used as an appetite suppressant. It is typically prescribed for individuals who are at increased medical risk because of their weight, as opposed to cosmetic weight loss. Phentermine is sold either as an immediate-release formulation (Adipex®) or as a slow-release resin (Ionamin®, Duromine® in Australia and New Zealand).

History

Phentermine is one of two drugs in the Fen-phen anti-obesity medication, the other being fenfluramine or dexfenfluramine. Fenfluramine was withdrawn from the U.S. market in 1997 after reports of valvular heart disease and pulmonary hypertension.

Phentermine is still available by itself in most countries, including the U.S. However, because it is similar to the amphetamines, individuals may develop an addiction to it. Hence, it is classified as a controlled substance in many countries. Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances (PDF file). In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act.

Mechanism of action

Phentermine, as many other prescription drugs, works with neurotransmitters in the brain. It is a centrally-acting stimulant chemically related to the amphetamines. It stimulates neuron bundles to release a particular group of neurotransmitters known as catecholamines; these include dopamine, epinephrine (also known as adrenalin), and norepinephrine (noradrenaline). The anorectic activity seen with these compounds would thus seem likely due to this effect on Central Nervous System, which is consistent with current knowledge about Central Nervous System systems and feeding behavior. This is the same mechanism of action as other stimulant appetite suppresants such as diethylpropion, and phendimetrazine.

The neurotransmitters signal a fight-or-flight response in the body which, in turn, puts a halt to the hunger signal. As a result, it causes a loss in appetite because the brain does not receive the hunger message.

Clinical use

Generally, it is recommended by the 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. However, recommendations limiting its use for short-term treatment may be controversial. One reason given behind limiting its use to 12 weeks is drug tolerance, whereby phentermine loses its appetite-suppressing effects after the body adjusts to the drug. On the contrary, it has been shown that phentermine did not lose effectiveness in a 36-week trial (PMID 11054601). Due to the risk of insomnia, it is generally recommended that the drug be taken either before breakfast or 1-2 hours after breakfast.

Side effects

Generally, phentermine appears to be relatively well tolerated.^[1] It can produce side effects consistent with its catecholaminereleasing properties, e.g., tachycardia, increased alertness, 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, individuals taking this drug on a long-term basis may develop euphoria and a psychological addiction to it.

Contraindications

Phentermine should generally be avoided in patients with:

• Agitation
• Allergy/Hypersensitivity to other sympathomimetic amines
• Atherosclerosis
• Cardiovascular disease
• Glaucoma
• High blood pressure
• Hyperthyroidism
• Previous history of drug abuse

Additionally, this drug should not be used at the same time or within 14 days following the use of monoamine oxidase inhibitors.

Internet Notoriety

Recently, phentermine has drawn the ire of many internet users. The medication is one of the most commonly used terms in spam e-mails and bulletin board postings by bots.

Related Article

• Obesity
• Anti-obesity drug