Substituted amphetamines are a class of compounds based upon the

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

structure; it includes all

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

compounds which are formed by replacing, or substituting, one or more

hydrogen atom A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively charged proton and a single negatively charged electron bound to the nucleus by the Coulomb force. Atomic hydrogen cons ...

s in the amphetamine core structure with

substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as '' side ...

s. The compounds in this class span a variety of pharmacological subclasses, including

stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

, empathogens, and

hallucinogens Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categoriz ...

, among others. Examples of substituted amphetamines are amphetamine (itself),

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...

ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...

cathinone Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the mai ...

phentermine Phentermine ( phenyl- tertiary-butyl amine), with several brand names including Ionamin and Sentis, is a medication used together with diet and exercise to treat obesity. It is taken by mouth for up to a few weeks at a time, after which the ben ...

mephentermine Mephentermine is a cardiac stimulant. It has been used as a treatment for low blood pressure. Mephentermine belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of heart failure. Me ...

bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

methoxyphenamine Methoxyphenamine (trade names ASMI, Euspirol, Orthoxine, Ortodrinex, Proasma), also known as 2-methoxy-''N''-methylamphetamine (OMMA), is a β-adrenergic receptor agonist of the amphetamine class used as a bronchodilator. It acts as an anti-inf ...

selegiline Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or ...

, amfepramone (diethylpropion),

pyrovalerone (Centroton, 4-Methyl-β-keto-prolintane, Thymergix, O-2371) is a psychoactive drug with stimulant effects via acting as a norepinephrine-dopamine reuptake inhibitor (NDRI), and is used for the clinical treatment of chronic fatigue or letharg ...

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

(ecstasy), and DOM (STP). Some of amphetamine's substituted derivatives occur in nature, for example in the leaves of ''

Ephedra Ephedra may refer to: * Ephedra (medicine), a medicinal preparation from the plant ''Ephedra sinica'' * ''Ephedra'' (plant), genus of gymnosperm shrubs See also * Ephedrine Ephedrine is a central nervous system (CNS) stimulant that is of ...

'' and khat plants. Amphetamine was first produced at the end of the 19th century. By the 1930s,

and some of its

compounds found use as decongestants in the symptomatic treatment of

colds The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...

and also occasionally as psychoactive agents. Their effects on the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

are diverse, but can be summarized by three overlapping types of activity: psychoanaleptic,

hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

and empathogenic. Various substituted amphetamines may cause these actions either separately or in combination.

Partial list of substituted amphetamines

Prodrugs of amphetamine/methamphetamine

A variety of

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the dru ...

s of

and/or

exist, and include

amfecloral Amfecloral (INN), also known as amphecloral (USAN), is a stimulant drug of the phenethylamine and amphetamine chemical classes that was used as an appetite suppressant under the trade name Acutran, but is now no longer marketed. It was classif ...

, amphetaminil,

benzphetamine Benzphetamine (brand name Didrex) is a substituted amphetamine used short-term along with a doctor-approved, reduced-calorie diet, exercise, and behavioral program for weight loss. It is prescribed for obesity to people who have been unable to lo ...

clobenzorex Clobenzorex (Asenlix, Dinintel, Finedal, Rexigen) is a stimulant drug of the amphetamine chemical class used as an appetite suppressant. The drug is legally distributed in Mexico under the trade name Asenlix by Aventis. Chemically, clobenzorex ...

, D-deprenyl,

dimethylamphetamine Dimethylamphetamine (Metrotonin), also known as dimetamfetamine (INN), dimephenopan and ''N'',''N''-dimethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes. Dimethylamphetamine has weaker stimulant effects ...

ethylamphetamine Etilamfetamine (trade names Apetinil and Adiparthrol; also known as ''N''-ethylamphetamine) is a stimulant drug of the phenethylamine and amphetamine chemical classes. It was invented in the early 20th century and was subsequently used as an ano ...

fencamine Fencamine (Altimina, Sicoclor) is a psychostimulant drug of the amphetamine class. It is closely related to fenethylline Fenethylline ( BAN, USAN) is a codrug of amphetamine and theophylline and a prodrug to both. It is also spelled ph ...

fenethylline Fenethylline ( BAN, USAN) is a codrug of amphetamine and theophylline and a prodrug to both. It is also spelled phenethylline and fenetylline (INN); other names for it are amphetaminoethyltheophylline and amfetyline. The drug was marketed for ...

fenproporex Fenproporex (Perphoxene) (N-2-Cyanoethylamphetamine) (3-(1-phenylpropan-2-ylamino)propanenitrile) (3- 1-Methyl-2-Phenylethyl)aminoropiononitrile) is a stimulant drug of the phenethylamine and amphetamine chemical classes that was developed in th ...

furfenorex Furfenorex (Frugalan), also known as furfurylmethylamphetamine, is a stimulant drug which was developed in the 1960s and used as an appetite suppressant. It produces methamphetamine as a metabolite, and has been withdrawn from the market due to ...

lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...

mefenorex Mefenorex (Rondimen, Pondinil, Anexate) is a stimulant drug which was used as an appetite suppressant. It is an amphetamine derivative which was developed in the 1970s and used for the treatment of obesity. Mefenorex produces amphetamine as a me ...

prenylamine Prenylamine (Segontin) is a calcium channel blocker of the amphetamine chemical class that was used as a vasodilator in the treatment of angina pectoris. History Prenylamine was introduced in the 1960s by German manufacturer Albert-Roussel ph ...

, and

Structure

Amphetamines are a subgroup of the

substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by ...

class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...

and sometimes

ethyl group In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry's nomenclature of organic chemistry for a saturated ...

s at the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

and

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

sites:Schatzberg, p.843

History

was used 5000 years ago in China as a

medicinal plant Medicinal plants, also called medicinal herbs, have been discovered and used in traditional medicine practices since prehistoric times. Plants synthesize hundreds of chemical compounds for various functions, including defense and protection ag ...

; its active ingredients are

alkaloids Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

ephedrine,

pseudoephedrine Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses. It was first charact ...

, norephedrine (

phenylpropanolamine Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to cont ...

) and norpseudoephedrine (

cathine -norpseudoephedrine, also known as cathine and (+)-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant. Along with cathinone, it is found naturally in ''Catha edulis'' (kh ...

). Natives of

Yemen Yemen (; ar, ٱلْيَمَن, al-Yaman), officially the Republic of Yemen,, ) is a country in Western Asia. It is situated on the southern end of the Arabian Peninsula, and borders Saudi Arabia to the north and Oman to the northeast and ...

and

Ethiopia Ethiopia, , om, Itiyoophiyaa, so, Itoobiya, ti, ኢትዮጵያ, Ítiyop'iya, aa, Itiyoppiya officially the Federal Democratic Republic of Ethiopia, is a landlocked country in the Horn of Africa. It shares borders with Eritrea to the ...

have a long tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, cathine.

Amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

was first synthesized in 1887 by

Romania Romania ( ; ro, România ) is a country located at the crossroads of Central Europe, Central, Eastern Europe, Eastern, and Southeast Europe, Southeastern Europe. It borders Bulgaria to the south, Ukraine to the north, Hungary to the west, S ...

n chemist

Lazăr Edeleanu Lazăr Edeleanu (; 1 September 1861, Bucharest – 7 April 1941, Bucharest) was a Romanian chemist of Jewish origin.Snow, p. 1 MDMA was produced in 1912 (in 1914, according to other sources) as an intermediate product. However, this synthesis also went largely unnoticed.Goldfrank, p. 1125 In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine,

dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...

, were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French (now part of

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

), as a medicine (

Benzedrine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

) for

cold Cold is the presence of low temperature, especially in the atmosphere. In common usage, cold is often a subjective perception. A lower bound to temperature is absolute zero, defined as 0.00K on the Kelvin scale, an absolute thermodynamic ...

s and

nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathin ...

. Subsequently, amphetamine was used in the treatment of

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...

and

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

.Goldfrank, p. 1119 The "reinforcing" effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936. Amph salts

During

World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...

, amphetamines were used by the German military to keep their tank crews awake for long periods, and treat depression. It was noticed that extended rest was required after such artificially induced activity. The widespread use of substituted amphetamines began in postwar

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...

and quickly spread to other countries. Modified "designer amphetamines", such as MDA and PMA, have gained in popularity since the 1960s. In 1970, the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

adopted "the Controlled Substances Act" that limited non-medical use of substituted amphetamines. Street use of PMA was noted in 1972. MDMA emerged as a substitute for MDA in the early 1970s. American chemist

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymetha ...

first synthesized the drug in 1976 and through him the drug was briefly introduced into psychotherapy. Recreational use grew and in 1985 MDMA was banned by the US authorities in an emergency scheduling initiated by the

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic en ...

. Since the mid-1990s, MDMA has become a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as ecstasy.Goldfrank, p. 1121 Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder (PTSD).

Legal status

References

Bibliography

* * * * * * * *

External links

* {{DEFAULTSORT:Substituted Amphetamine Amphetamine Chemical classes of psychoactive drugs de:Phenylethylamine#Amphetamine