Substituted amphetamines are a class of compounds based upon the amphetamine 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 substituents. The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, 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. Meth ...

, ephedrine, cathinone, phentermine, mephentermine, bupropion,

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-infl ...

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,

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 desired ...

(ecstasy), and DOM (STP). Some of amphetamine's substituted

derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics *Brzozowski derivative in the theory of formal languages *Formal derivative, an ...

occur in nature, for example in the leaves of '' Ephedra'' and khat plants. Amphetamine was first produced at the end of the 19th century. By the 1930s, amphetamine and some of its

compounds found use as decongestants in the symptomatic treatment of colds 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 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 prodrugs of amphetamine 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 classifi ...

, amphetaminil, benzphetamine,

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, clobenzor ...

, D-deprenyl, dimethylamphetamine, ethylamphetamine, fencamine, fenethylline, fenproporex, furfenorex, lisdexamfetamine, mefenorex, prenylamine, and

Structure

Amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by methyl and sometimes ethyl groups 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 su ...

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 hydroge ...

sites:Schatzberg, p.843

History

Ephedra was used 5000 years ago in China as a medicinal plant; its active ingredients are alkaloids ephedrine, pseudoephedrine, norephedrine ( phenylpropanolamine) 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'' (kha ...

). 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 an ...

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 Er ...

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 was first synthesized in 1887 by

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

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, were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma 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 corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

), as a medicine ( Benzedrine) for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy,

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, orthostatic hypotension,

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 electrical ...

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 becom ...

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. Predomina ...

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 ho ...

.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 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 primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...

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 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 Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...

. 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