Meprobamate
Systematic (IUPAC) name
[2-(carbamoyloxymethyl)-2-methyl-pentyl] carbamate
Identifiers
CAS number	57-53-4
ATC code	N05BC01
PubChem	4064
DrugBank	APRD01095
Chemical data
Formula	C9H18N2O4
Mol. mass	218.250 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	10 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D(US) IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula is an easy way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... This article is about the chemistry of hydrogen. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... This article is about the chemical element and its most stable form, or dioxygen. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is the largest internal organ in the human body, and is an organ present in vertebrates and some other animals. ... The biological half-life of a substance is the time required for half of that substance to be removed from an organism by either a physical or a chemical process. ... The kidneys are important excretory organs in vertebrates. ... The kidneys are the organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Legal status	Schedule IV(US) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... This box:      The Controlled Substances Act (CSA) 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. ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Routes	Oral

Meprobamate (marketed under the brand names Miltown by Wallace Laboratories, Equanil by Wyeth, and Meprospan) is a carbamate derivative which is used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benzodiazepines. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Carbamates are a group of organic compounds sharing a common functional group with the general structure -NH(CO)O-. More precisely the carbamate group is considered an amide group with an alkoxy or hydroxy functional group next to the carbonyl group. ... An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , often abbreviated to benzos) are a class of sedative hypnotic psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ...

History

Meprobamate was first synthesized by Bernard John Ludwig and Frank Milan Berger, MD, at Carter Products in May 1950. Wallace Laboratories, a subsidiary of Carter Products, bought the license and named it Miltown after the village Milltown in New Jersey. Launched in 1955, it rapidly became a best seller and famous in the popular media as "Happy Pills".^{[citation needed]} In the mid-1940s, Dr. Berger was working in a laboratory of a British drug company, when he noticed that a chemical with which he was working had a sedative effect in small laboratory animals (rodents). Dr Berger subsequently referred to this sedating or “tranquilizing” effect in a now-historic article, published by The British Journal of Pharmacology in 1946. After moving Wallace Laboratories in New Jersey, Dr. Berger and a chemist, Bernard Ludwig, synthesized a chemically-related tranquilizing compound, meprobamate, which was introduced under the trade name Miltown, the village near their lab at Wallace. Milltown is a Borough in Middlesex County, New Jersey, United States. ... This article is about the U.S. state. ...

A December 1955 study of 101 patients at the Mississippi State Hospital in Whitfield, Mississippi, found Meprobamate useful in the alleviation of mental symptoms. 3% of the patients made a complete recovery, 29% were greatly improved, and 50% were somewhat better. 18% realized little change. Self-destructive patients became cooperative and calmer, and experienced a resumption of logical thinking. In 50% of the cases relaxation brought about more favorable sleep habits. Hydrotherapy and all types of shock treatment were halted.^[1] Meprobamate was found to help in the treatment of alcoholics by 1956.^[2] Dr. Berger, clinical director of Wallace Laboratories (who died on March 16, 2008, aged 94^[3]), described it as a relaxant of the central nervous system, whereas other tranquilizers suppressed it. A University of Michigan study found that Meprobamate affected driving skills. Patients reported being able to relax more even though they continued to feel tense (needs clarification). The disclosures came at a special scientific meeting at the Barbizon Plaza Hotel in New York City, at which Aldous Huxley addressed an evening session. He predicted the development of many chemicals capable of changing the quality of human consciousness, in the next few years.^[4] Year 1955 (MCMLV) was a common year starting on Saturday (link displays the 1955 Gregorian calendar). ... For hydrotherapy in dogs, see Canine hydrotherapy. ... This article is about the 1981 musical comedy film. ... A car from 1956 Year 1956 (MCMLVI) was a leap year starting on Sunday (link will display full calendar) of the Gregorian calendar. ... A diagram showing the CNS: 1. ... A sedative is a drug that depresses the central nervous system (CNS), which causes calmness, relaxation, reduction of anxiety, sleepiness, slowed breathing, slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... The University of Michigan, Ann Arbor (U of M, UM, U-M or simply Michigan) is a coeducational public research university in the state of Michigan. ... New York, New York and NYC redirect here. ... Aldous Leonard Huxley (July 26, 1894 – November 22, 1963) was an English writer and one of the most prominent members of the famous Huxley family. ...

Miltown was sometimes referred to incorrectly as chlorpromazine. One such instance of this was a review by author Frank Slaughter of the book, A Man Against Insanity, by Paul de Kruif.^[5] Chlorpromazine was the first antipsychotic drug, used during the 1950s and 1960s. ... Frank Gill Slaughter (1908-2001), pseudonym C.V. Terry, was an American bestseller novelist and physician, whose books sold more than 60 million copies. ... Paul de Kruif, or Paul Henry De Kruif ( 1890 - 1971 ) was an American microbiologist and author. ...

In January 1960 Carter Products, Inc., makers of Miltown and American Home Products Corporation, which marketed Equanil, were charged with having conspired to monopolize the market in mild tranquilizers. It was revealed that in 1948 the sale of Meprobamate earned $40,000,000 for the defendants. Of this amount American Home Products accounted for approximately 2/3 and Carter about 1/3. The U.S. Government sought an order mandating that Carter make its Meprobamate patent available at no charge to any company desiring to use it.^[6] Year 1960 (MCMLX) was a leap year starting on Friday (link will display full calendar) of the Gregorian calendar. ... Year 1948 (MCMXLVIII) was a leap year starting on Thursday (link will display the 1948 calendar) of the Gregorian calendar. ...

In April 1965 Meprobamate was removed from the list of tranquilizers when experts ruled that the drug was a sedative instead. U.S. Pharmacopoeia published the ruling. At the same time the Medical Letter disclosed that Meprobamate could be addictive at dosage levels not much above recommended.^[7] In December 1967 Meprobamate was placed under abuse control amendments to the Food, Drug and Cosmetic Act. Records on production and distribution were required to be kept. Limits were placed on prescription duration and refills.^[8] Year 1965 (MCMLXV) was a common year starting on Friday (link will display full calendar) of the 1965 Gregorian calendar. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Year 1967 (MCMLXVII) was a common year starting on Sunday (link will display full calendar) of the 1967 Gregorian calendar. ...

Production continued throughout the 1960s but by 1970 it was listed as a controlled substance after it was discovered to cause physical and psychological dependence. Nevertheless, its place in the history of pharmacology and therapeutics is cemented, as the drug is considered to be the forerunner of the modern-era benzodiazepine class of anti-anxiety and sedative/hypnotic drugs (as the pharmacological actions of the benzodiazepines on the central nervous system mimic those of meprobamate). The first member of the benzodiazepine class, chlordiazepoxide (synthesized by the Swiss firm, Hoffman LaRoche and marketed as Librium when introduced in 1960) gave rise to the drug still commonly used today — diazepam — better known by its original brand-name, Valium (also introduced and still marketed by Roche Products). The significance of meprobamate and the benzodiazepines lies in the fact that these drugs, despite being habit-forming, essentially replaced the widely-used and potentially-lethal class of sedatives, the barbiturates. The role of barbiturates today is virtually restricted to the emergency treatment of some forms of (usually epileptic) seizures in infants. Alprazolam 2 mg tablets The benzodiazepines (pronounced , often abbreviated to benzos) are a class of sedative hypnotic psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... Chlordiazepoxide (pronounced [ˈklɔːrËŒdaɪəzepˈoksaɪd], marketed under the trade name Librium®) is a sedative/hypnotic drug which is a benzodiazepine derivative. ... Diazepam (IPA: ), first marketed as Valium by Hoffmann-La Roche) is a benzodiazepine derivative drug. ... Barbiturates are drugs that acts as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ...

Pharmacology

Although it was marketed as being safer, meprobamate has most of the pharmacological effects and dangers of the barbiturates (though it is less sedating at effective doses). It is reported to have some anticonvulsant properties against absence seizures, but can exacerbate generalized tonic-clonic seizures. Barbituric acid, the basic structure of all barbiturates Barbiturates are drugs that act as central nervous system depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ...

Meprobamate's mechanism of action is not known. It has been shown in animal studies to have effects at multiple sites in the central nervous system, including the thalamus and limbic system. Meprobamate binds to GABA_A receptors which interrupt neuronal communication in the reticular formation and spinal cord, causing sedation and altered perception of pain. The thalamus (from Greek θάλαμος = bedroom, chamber, IPA= /ˈθæləməs/) is a pair and symmetric part of the brain. ... The limbic system is a historically defined set of brain structures that support a variety of functions including emotion and memory. ... The GABAA receptor is one of the three ligand-gated ion channels responsible for mediating the effects of Gamma-AminoButyric Acid (GABA), the major inhibitory neurotransmitter in the brain. ... The reticular formation is a part of the brain which is involved in stereotypical actions, such as walking, sleeping, and lying down. ... The Spinal cord nested in the vertebral column. ...

Related drugs include carisoprodol (a prodrug of meprobamate) and tybamate. Carisoprodol is a centrally-acting skeletal muscle relaxant whose active metabolite is meprobamate. ... A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... Tybamate is an anxiolytic. ...

Indications

Meprobamate is used for treatment of anxiety disorders or for short-term relief of anxiety.

It has also been used off-label as a sedative. However, it is currently only licensed as an anxiolytic, and is not used as often as the benzodiazepines for this purpose. The term off-label refers to the use of a drug for a medical condition other than for which it was officially approved and marketed. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ...

Meprobamate is available in 200mg and 400mg tablets for oral administration. Meprobamate is also a component of the combination drug Equagesic (discontinued in the UK in 2002) acting as a muscle relaxant. Usage Equagesic (pronounced ) is a combination drug indicated for short-term pain treatment accompanied by tension and/or anxiety in patients with musculoskeletal disease or tension headache. ... A muscle relaxant is a drug which decreases the tone of a muscle. ...

Overdose

Symptoms of meprobamate overdose include: coma, drowsiness, loss of muscle control, severely impaired breathing, shock, sluggishness, and unresponsiveness. Death has been reported with ingestion of as little as 12g of meprobamate and survival with as much as 40g.

Legal Issues

Meprobamate is a Schedule IV drug under the Convention on Psychotropic Substances. Meprobamate may cause GI concretions in overdose; therefore, charcoal should be considered even after 4 hours or if levels are rising. The Controlled Substances Act (CSA), Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, is the legal foundation of the United States governments fight against the abuse of drugs and other substances. ... Convention on Psychotropic Substances Opened for signature February 21, 1971 in Vienna Entered into force August 16, 1976 Conditions for entry into force 40 ratifications Parties 175 The Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. ...

References

1. ^ New Hope Arises On Cancer Serum, New York Times, December 28, 1955, Page 21.
2. ^ Alcohol Peril Found In Drugs, New York Times, April 1, 1956, Page 28.
3. ^ Frank Berger, 94, Miltown Creator, Dies, New York Times, March 21, 2008.
4. ^ Behavior Drugs Now Envisioned, New York Times, October 19, 1956, Page 29.
5. ^ Letters To The Editor: Drugs, New York Times, April 7, 1957, Page 263.
6. ^ Trust Suit Names 2 Drug Concerns, New York Times, January 28, 1960, Page 1.
7. ^ Miltown Off List Of Tranquilizers, New York Times, April 22, 1965, Page 34.
8. ^ Tranquilizer Is Put Under U.S. Curbs; Side-Effects Noted, New York Times, December 6, 1967, Page 35.

• Barondes, Samuel H. Better Than Prozac. New York: Oxford University Press, 2003. ISBN 0-19-515130-5.
• A History of Psychiatry: From the Era of the Asylum to the Age of Prozac by Edward Shorte. John Wiley and Sons.
• List of psychotropic substances under international control.
• The Comparative Toxicogenomics Database: Meprobamate.
• BIAM: Meprobamate (French).

The New York Times is an internationally known daily newspaper published in New York City and distributed in the United States and many other nations worldwide. ...

External links

• RxList.com - Meprobamate