Phentermine
Encyclopedia
Phentermine, a contraction of "phenyl-tertiary-butylamine
", is a psychostimulant drug
of the phenethylamine
class, chemically related 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.
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 palpitation
s, 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.
Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure.
Central Nervous System
Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache.
Gastrointestinal
Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances.
Allergic
Urticaria, endocrine Impotence, changes in libido.
Medical conditions which may interact with phentermine
Medicines which may interact
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.
(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.
or dexfenfluramine
and became known as 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 that nearly 30% of people taking fenfluramine or dexfenfluramine had abnormal valve findings. The FDA did not ask manufacturers to remove phentermine from the market.
Phentermine is still available by itself in most countries, including the U.S. However, because it is similar to amphetamines, it is classified as a controlled substance
in many countries (including Australia). 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 with other medication for obesity. The experimental appetite suppressant drug Qnexa is a mixture of Phentermine and Topiramate
. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee reviewed Qnexa on July 15, 2010. The committee voted narrowly against recommending approval.
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
", is a psychostimulant drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
class, chemically related to amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
. 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.
Adverse effects
Generally, phentermine appears to be relatively well tolerated. It can produce side effects consistent with its catecholamine-releasingproperties, 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
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
. It may also cause palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
s, restlessness, and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Additionally, phentermine has the potential to cause psychological dependence. After short term use, tolerance begins and can be followed by rebound weight gain.
More common
CardiovascularPrimary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure.
Central Nervous System
Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache.
Gastrointestinal
Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances.
Allergic
Urticaria, endocrine Impotence, changes in libido.
Less common
- Convulsions (seizures)
- Fever
- Hallucinations
- Hostility with urge to attack
- Irregular blood pressure
- Lightheadedness or fainting
- Periods of mania followed by period of depression
- Tremors, trembling or shaking
- Overactive reflexes
- Panic
- Restlessness
- Severe nausea, vomiting or diarrhea
- Stomach cramps
- Weakness
- Constipation
Cautions
People with the following should not use phentermine:- An allergyAllergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
to any ingredient in Phentermine or other sympathomimetics (e.g., pseudoephedrinePseudoephedrinePseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent....
) - Are also taking amphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(i.e. Adderall, Dexedrine, Vyvanse), bupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
(WellButrin), dexfenfluramineDexfenfluramineDexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...
, fenfluramineFenfluramineFenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
, furazolidoneFurazolidoneFurazolidone is a nitrofuran antibacterial. It is marketed by Roberts Laboratories under the brand name Furoxone and by GlaxoSmithKline as Dependal-M.-Uses:It is used to treat diarrhoea and enteritis caused by bacteria or protozoan infections....
, guanadrelGuanadrelGuanadrel is an antihypertensive agent. It is used in the form of its sulfate.-Mechanism of action:Guanadrel is a postganglionic adrenergic blocking agent...
, guanethidineGuanethidineGuanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself , and uptake is essential for the drug's action...
, or have taken a monoamine oxidase inhibitorMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI) (e.g., phenelzine, in the last 14 days) - Have severe high blood pressure, an overactive thyroid, glaucomaGlaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, heart or blood vessel disease, or severe narrowing of the blood vessels - Are in an agitated state, or have a history of substance abuseSubstance abuseA substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
Medical conditions which may interact with phentermine
- Are pregnant, planning to become pregnant, or are breast-feeding
- Are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
- Have allergies to medicines, foods, or other substances
- Have a brain or spinal cord disorder, hardening of the arteries, high blood pressure, diabetes, or high cholesterol or lipid levels
Medicines which may interact
- Dexfenfluramine, fenfluramine, furazolidone, or MAOIs (e.g., phenelzine) because 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) because their effectiveness may be decreased by phentermine
- Antacids: Antacids may decrease the excretion of phentermine.
- Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide): Carbonic anhydrase inhibitors 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
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, a neurotransmitter or chemical messenger that signals a fight-or-flight response
Fight-or-flight response
The fight-or-flight response was first described by Walter Bradford Cannon....
, 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
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, but to a much lesser extent than that of norepinephrine.
Dosing and administration
Generally, it is recommended by the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(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
Dieting
Dieting is the practice of eating food in a regulated fashion to achieve or maintain a controlled weight. In most cases dieting is used in combination with physical exercise to lose weight in those who are overweight or obese. Some athletes, however, follow a diet to gain weight...
and exercise.
History
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, however 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 in 1959 there have been almost no clinical studies performed. The most recent study was in 1990 which combined phentermine with fenfluramineFenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
or dexfenfluramine
Dexfenfluramine
Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...
and became known as Fen-Phen
Fen-phen
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity treatment that utilizes two anorectics. Fenfluramine, its S-enantiomer dexfenfluramine, and a few other serotonin agonists were shown to cause potentially fatal pulmonary hypertension and heart valve...
.
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 that nearly 30% of people taking fenfluramine or dexfenfluramine had abnormal valve findings. The FDA did not ask manufacturers to remove phentermine from the market.
Phentermine is still available by itself in most countries, including the U.S. However, because it is similar to amphetamines, it is classified as a controlled substance
Controlled substance
A controlled substance is generally a drug or chemical whose manufacture, possession, or use are regulated by a government. This may include illegal drugs and prescription medications ....
in many countries (including Australia). Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
. In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
. In contrast, amphetamine preparations are classified as Schedule II controlled substances.
Phentermine is being studied with other medication for obesity. The experimental appetite suppressant drug Qnexa is a mixture of Phentermine and Topiramate
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee reviewed Qnexa on July 15, 2010. The committee voted narrowly against recommending approval.
Trade names
- Adipex P (Immediate release)
- Adiphene (India)
- Anoxine-AM
- Ionamin (Slow Release Resin, Australia, discontinued in the US)
- Duromine (Slow Release Resin, New Zealand, Australia & South Africa)
- Metermine (Slow Release Resin, Australia)
- Mirapront
- Obephen
- Obermine
- Obestin-30
- Phentremine
- Phentrol
- Phenterex
- Phentromin
- Pro-Fast SA
- Qnexa (with TopiramateTopiramateTopiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
) - Redusa
- Panbesy
- Phentermine Trenker
- Obenix
- Oby-Trim
- Teramine
- Zantryl
- Sinpet (MX)
- Supremin (PH)
- Umine (NZ)
- Weltmine (KP)
Chemistry
- BenzaldehydeBenzaldehydeBenzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
and 3-nitropropane are cross-reacted in a variant of the Henry reaction - The nitroNitro-Chemistry:*Nitroglycerin, an explosive chemical compound*Nitromethane, the simplest organic nitro compound; also used to fuel high-performance internal-combustion engines*Nitrous oxide, "laughing gas", used in some dental procedures as an anaesthetic...
group is reduced with hydrogen gas over Raney nickelRaney nickelRaney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...
catalyst. - The hydroxyl group is chlorinated with thionyl chlorideThionyl chlorideThionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
to yield 2-amino-2-methyl-1-phenylpropylchloride. - This is reduced with hydrogen gas over a palladium on calcium carbonate catalyst to yield the product, phentermine.