Amfecloral (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...
) or amphecloral (
USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島）
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to t ...
) is a
combination drug
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...
containing a
central nervous system (CNS) stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
and
anorectic
An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...
drug,
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
, as well as a
CNS depressant and
sedative
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
-
hypnotic
A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...
,
chloral hydrate
Chloral hydrate is a geminal diol with the formula . It was first used as a sedative and hypnotic in Germany in the 1870s. Over time it was replaced by safer and more effective alternatives but it remained in use in the United States until at ...
.
Widely used for its
anorectic
An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...
properties, amfecloral was approved by the
United States
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
as an
anti-obesity drug
Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and con ...
and
marketed
Marketing is the act of acquiring, satisfying and retaining customers. It is one of the primary components of business management and commerce.
Marketing is usually conducted by the seller, typically a retailer or manufacturer. Products can ...
and distributed under the
brand name
A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...
Acutran. Upon 1962 passage of the
Kefauver-Harris Amendment, pressure grew to withdraw the product from the market, and in 1973, production ceased for Acutran and its generic formulation, concurrent with similar combination anorectics,
Desbutal (
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
-
pentobarbital
Pentobarbital (US) or pentobarbitone (British and Australian) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but ...
) and
Obetrol (
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
-
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
).
Naming and Classification
The British Pharmacopoeia Commission approved the name ''amfecloral'' in 1970. It is classified as a
combination drug
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...
constituting active ingredients belong to the
phenethylamine
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...
and
ethanol
Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
chemical class
Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classi ...
es, similar to many combination drugs in widespread use at the time for various indications, including
Desbutal,
Dexamyl
Dexamyl (or Drinamyl in the UK) was the brand name of a combination drug composed of amobarbital (previously called amylbarbitone) and dextroamphetamine (Dexedrine) within the same pill. It was widely abused and is no longer manufactured.
First ...
(also branded ''AmoDex''), and
Obetrol.
Amfecloral belongs to the
phenethylamine
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...
and
substituted amphetamine
Substituted amphetamines, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...
chemical class
Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classi ...
es.
Synthesis and Pharmacology
The raw ingredients used in manufacturing it were
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
and
chloral hydrate
Chloral hydrate is a geminal diol with the formula . It was first used as a sedative and hypnotic in Germany in the 1870s. Over time it was replaced by safer and more effective alternatives but it remained in use in the United States until at ...
.
Upon ingestion and metabolization, amfecloral is metabolized as dextroamphetamine and
chloral hydrate
Chloral hydrate is a geminal diol with the formula . It was first used as a sedative and hypnotic in Germany in the 1870s. Over time it was replaced by safer and more effective alternatives but it remained in use in the United States until at ...
, as well as converting into
levoamphetamine
Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination drug, combination with dextroam ...
, the R
enantiomer
In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
of
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
. Amphetamine is a
stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
, whereas chloral hydrate is a
sedative/hypnotic drug.
The extent of metabolism and in-vivo contribution of a chloral hydrate metabolism to its purported "little to no stimulant activity" is unknown.
History
Combination Drugs in the Twentieth Century
Acutran was one of several brands, amfecloral one of several formulations distributed as
anorectic
An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...
combination drugs
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. F ...
comprising a CNS
stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
and a CNS
depressant
Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various ...
–respectively known as "uppers" and "downers"
in common parlance, conjoined in the form of one pill: others included
Desbutal (
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
-
pentobarbital
Pentobarbital (US) or pentobarbitone (British and Australian) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but ...
) and Obetrol (meth-dexamphetamine), both of which were discontinued concurrent to Acutran in 1973;
Eskatrol (
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
and the
neuroleptic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizoph ...
compazine, discontinued 1981), in addition to
Dexamyl
Dexamyl (or Drinamyl in the UK) was the brand name of a combination drug composed of amobarbital (previously called amylbarbitone) and dextroamphetamine (Dexedrine) within the same pill. It was widely abused and is no longer manufactured.
First ...
(dextamphetamine-
amylbarbitone).
Efficacy and Tolerability
A review from 1970 specified that amfecloral was unique among amphetamine-like substances in that it displayed little to no stimulant activity, likely due to the powerful sedating effects of chloral hydrate, the same claims were not made of the other combination medications.
The extent of metabolism and in-vivo contribution of a chloral hydrate metabolism to its purported "little to no stimulant activity" is unknown.
Discontinuation
Following increased scrutiny of combination medications comprising
psychostimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...
and
sedative
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
components with the 1962 passage of the
Kefauver-Harris Amendment, then the
Controlled Substances Act of 1970, Acutran was withdrawn from the U.S. pharmaceutical market and ceased production, alongside
Desbutal (methamphetamine-pentobarbital) and
Obetrol (methamphetamine-dextroamphetamine), all three of which were fully discontinued by the end of 1973.
See also
*
Amfetaminil
*
Clobenzorex
*
Desbutal (also discontinued 1973)
*
Dexamyl
Dexamyl (or Drinamyl in the UK) was the brand name of a combination drug composed of amobarbital (previously called amylbarbitone) and dextroamphetamine (Dexedrine) within the same pill. It was widely abused and is no longer manufactured.
First ...
*
Eskatrol
*
Obetrol (also discontinued 1973)
References
Anorectics
Substituted amphetamines
Prodrugs
Trichloromethyl compounds
Norepinephrine-dopamine releasing agents
{{nervous-system-drug-stub