Methaqualone

Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude (/ˈkweɪluːd/ KWAY-lood) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under the brand name Mandrax, which contained 250 mg methaqualone and 25 mg diphenhydramine within the same tablet, mostly in Europe. Commercial production of methaqualone was halted in the mid-1980s due to widespread abuse and addictiveness. It is a member of the quinazolinone class.

Methaqualone
Clinical data
Pronunciation/mɛθəˈkweɪloʊn/
Trade namesBon-Sonnil, Dormogen, Dormutil, Mequin, Mozambin, Pro Dorm, Quaalude, Somnotropon, Torinal, Tuazolona
Methaqualone hydrochloride:
Cateudyl, Dormir, Hyptor, Melsed, Melsedin, Mequelon, Methasedil, Nobadorm, Normorest, Noxybel, Optimil, Optinoxan, Pallidan, Parest, Parmilene, Pexaqualone, Renoval, Riporest, Sedalone, Somberol, Somnifac, Somnium, Sopor, Sovelin, Soverin, Sovinal, Toquilone, Toraflon, Tualone, Tuazol
ATC code
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • CA: Schedule III
  • DE: Anlage II (Authorized trade only, not prescriptible)
  • UK: Class B
  • US: Schedule I
  • UN: Psychotropic Schedule II
Pharmacokinetic data
Protein binding70–80%
Elimination half-lifeBiphasic (10–40; 20–60 hours)
Identifiers
IUPAC name
  • 2-Methyl-3-o-tolyl-4(3H)-quinazolinone;
    3,4-Dihydro-2-methyl-4-oxo-3-o-tolylquinazoline;
    2-Methyl-3-(2-methylphenyl)-4-(3H)-quinazolinone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.710
Chemical and physical data
FormulaC16H14N2O
Molar mass250.301 g·mol−1
3D model (JSmol)
Melting point113 °C (235 °F)
  • Cc1ccccc1-n1c(C)nc2ccccc2c1=O
  • InChI=1S/C16H14N2O/c1-11-7-3-6-10-15(11)18-12(2)17-14-9-5-4-8-13(14)16(18)19/h3-10H,1-2H3 Y
  • Key:JEYCTXHKTXCGPB-UHFFFAOYSA-N Y
  (verify)

The sedative–hypnotic activity of methaqualone was first noted in 1955. In 1962, methaqualone was patented in the United States by Wallace and Tiernan.[1] Its use peaked in the early 1970s for the treatment of insomnia, and as a sedative and muscle relaxant.

Methaqualone became increasingly popular as a recreational drug and club drug in the late 1960s and 1970s, known variously as "ludes" or "disco biscuits" due to its widespread use during the popularity of disco in the 1970s, or "sopers" (also "soaps") in the United States and Canada, and "mandrakes" and "mandies" in the United Kingdom, Australia and New Zealand. The substance was sold both as a free base and as a salt (hydrochloride).

Medical use

Methaqualone is a sedative that increases the activity of the GABA receptors in the brain and nervous system, similarly to benzodiazepines and barbiturates. When GABA activity is increased, blood pressure drops and breathing and pulse rates slow, leading to a state of deep relaxation. These properties explain why methaqualone was originally mainly prescribed for insomnia.[2]

Methaqualone was not recommended for use while pregnant and is in pregnancy category D.[3]

Overdose

An overdose can lead to nervous system shutdown, coma and death.[4] Additional effects are delirium, convulsions, hypertonia, hyperreflexia, vomiting, kidney failure, coma, and death through cardiac or respiratory arrest. It resembles barbiturate poisoning, but with increased motor difficulties and a lower incidence of cardiac or respiratory depression. The standard single tablet adult dose of Quaalude brand of methaqualone was 300 mg when made by Lemmon. A dose of 8000 mg is lethal and a dose as little as 2000 mg could induce a coma if taken with an alcoholic beverage.[5]

Pharmacology

Methaqualone peaks in the bloodstream within several hours, with a half-life of 20–60 hours. While the salt methaqualone hydrochloride is typically used clinically, methaqualone free-base was also marketed, namely as the methaqualone component of Mandrax, a combination drug which contained 250 mg methaqualone and 25 mg diphenhydramine within the same tablet. Oral dosage forms of methaqualone hydrochloride were manufactured as capsules, whereas oral dosage forms of methaqualone free-base were manufactured as tablets.

Regular users build up a physical tolerance, requiring larger doses for the same effect.

History

Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Husain Zaheer, who were conducting research on finding new antimalarial medications.[5][6][7] By 1965, it was the most commonly prescribed sedative in Britain, where it has been sold legally under the names Malsed, Malsedin, and Renoval. In 1965, a methaqualone/antihistamine combination was sold as the sedative drug Mandrax in Europe, by Roussel Laboratories (now part of Sanofi S.A.). In 1972, it was the sixth-bestselling sedative in the US,[8] where it was legal under the brand name Quaalude.

Quaalude in the United States was originally manufactured in 1965 by the Fort Washington, Pennsylvania, based pharmaceutical firm William H. Rorer, Inc. The drug name "Quaalude" is a portmanteau, combining the words "quiet interlude" and shared a stylistic reference to another drug marketed by the firm, Maalox.[9]

In 1978, Rorer sold the rights to manufacture Quaalude to the Lemmon Company of Sellersville, Pennsylvania. At that time, Rorer chairman John Eckman commented on Quaalude's bad reputation stemming from illegal manufacture and use of methaqualone, and illegal sale and use of legally prescribed Quaalude: "Quaalude accounted for less than 2% of our sales, but created 98% of our headaches."[5]

Both companies still regarded Quaalude as an excellent sleeping drug. Lemmon, well aware of Quaalude's public image problems, used advertisements in medical journals to urge physicians "not to permit the abuses of illegal users to deprive a legitimate patient of the drug". Lemmon also marketed a small quantity under another name, Mequin, so doctors could prescribe the drug without the negative connotations.[5]

The rights to Quaalude were held by the JB Roerig & Company division of Pfizer, before the drug was discontinued in the United States in 1985, mainly due to its psychological addictiveness, widespread abuse, and illegal recreational use.[10]

Society and culture

Brand names

It was sold under the brand name Quaalude and sometimes stylized "Quāālude" in the United States and Canada,[11] and Mandrax in the UK, South Africa, and Australia.

Regulation

Methaqualone was initially placed in Schedule I as defined by the UN Convention on Psychotropic Substances, but was moved to Schedule II in 1979.[12]

In Canada, methaqualone is listed in Schedule III of the Controlled Drugs and Substances Act and requires a prescription, but it is no longer manufactured. Methaqualone is banned in India.[13]

In the United States it was withdrawn from the market in 1983 and made a Schedule I drug in 1984.[14]

Recreational
A variety of methaqualone pills and capsules.

Methaqualone became increasingly popular as a recreational drug in the late 1960s and 1970s, known variously as "ludes" or "sopers" (also "soaps") in the United States and "mandrakes" and "mandies" in the UK, Australia and New Zealand. Sopor is a Latin word for sleep.

The drug was more tightly regulated in Britain under the Misuse of Drugs Act 1971 and in the U.S. from 1973. It was withdrawn from many developed markets in the early 1980s. In the United States it was withdrawn in 1983 and made a Schedule I drug in 1984. It has a DEA ACSCN of 2565 and in 2022 the aggregate annual manufacturing quota for the United States was 60[15] grams.

Mention of its possible use in some types of cancer and AIDS treatments has periodically appeared in the literature since the late 1980s. Research does not appear to have reached an advanced stage. The DEA has also added the methaqualone analogue mecloqualone (also a result of some incomplete clandestine syntheses) to Schedule I as ACSCN 2572, with a manufacturing quota of 30 g.[15]

Gene Haislip, the former head of the Chemical Control Division of the Drug Enforcement Administration (DEA), told the PBS documentary program Frontline, "We beat 'em." By working with governments and manufacturers around the world, the DEA was able to halt production and, Haislip said, "eliminated the problem".[16][17][18] Methaqualone was manufactured in the United States under the name Quaalude by the pharmaceutical firms Rorer and Lemmon with the numbers 714 stamped on the tablet, so people often referred to Quaalude as 714's, "Lemmons", or "Lemmon 7's".

Methaqualone was also manufactured in the US under the trade names Sopor and Parest. After the legal manufacture of the drug ended in the United States in 1982, underground laboratories in Mexico continued the illegal manufacture of methaqualone throughout the 1980s, continuing the use of the "714" stamp, until their popularity waned in the early 1990s. Drugs purported to be methaqualone are in a significant majority of cases found to be inert, or contain diphenhydramine or benzodiazepines.

Illicit methaqualone is one of the most commonly used recreational drugs in South Africa. Manufactured clandestinely, often in India, it comes in tablet form, but is smoked with marijuana. This method of ingestion is known as "white pipe".[19][20] It is popular elsewhere in Africa and in India.[20]

Chemical weapon – Project Coast

Illegal efforts to weaponize methaqualone have occurred. During the 1980s, the apartheid regime in South Africa ordered the covert manufacture of a ton of methaqualone at the front company Delta G Scientific Company, as part of a then-secret chemical weapons programme known as Project Coast.[21] Methaqualone was given the codename MosRefCat (Mossgas Refinery Catalyst). Details of this activity came to light during the 1998 hearings of the post-apartheid Truth and Reconciliation Commission.

See also

References
  1. US granted 3135659, Vithal SB, Campanella LA, Hays EE, "Hydroxy and Alkoxy Aryl Quinazolones", issued 1964-06-02, assigned to US Filter Wallace and Tiernan Inc
  2. "methaqualone reference". Enotes. Archived from the original on February 23, 2012.
  3. "Methaqualone in Pregnancy and Breastfeeding". TheDrugSafety.com. Archived from the original on 2012-10-02. Retrieved 15 August 2012.
  4. "recreational drugs tranquilizers". Drug Library EU. Archived from the original on 2013-03-02.
  5. Linder L (28 May 1981). Simons Jr DC, Mayer B, Nordyke R, Torrey A (eds.). "Quaalude manufacturer: Image hurt by street use". Lawrence Journal-World. Vol. 123, no. 148. Lawrence, Kansas, United States of America. Associated Press. p. 6. Retrieved 16 August 2013 – via Google Newspapers. Eckman/Fisher
  6. van Zyl EF (November 2001). "A survey of reported synthesis of methaqualone and some positional and structural isomers". Forensic Science International. 122 (2–3): 142–9. doi:10.1016/S0379-0738(01)00484-4. PMID 11672968.
  7. Kacker IK, Zaheer SH (1951). "Potential Analgesics. Part I. Synthesis of substituted 4-quinazolones". J. Ind. Chem. Soc. 28: 344–346.
  8. Foltz RL, Fentiman AG, Foltz RB (1980). GC/MS Assays for Abused Drugs in Body fluids (PDF). National Institutes on Drug Abuse. Vol. 32. Washington, D.C: United States Department of Health and Human Services. p. 39. PMID 6261132. Archived from the original (PDF) on 2004-10-22.
  9. "Dividends: Dropping the Last 'Lude". Time. 28 November 1983. Archived from the original on December 22, 2008. Retrieved 16 August 2013.
  10. Silverstein S. "Quaaludes Again". Captain Wayne's Mad Music.com.
  11. Rile K (1983). Winter Music (First ed.). Boston and Toronto: Little, Brown and Company. pp. 41, 59. ISBN 978-0-316-74657-1.
  12. Sandouk L. "green-lists". www.incb.org. Archived from the original on 2017-09-18. Retrieved 2017-09-06.
  13. "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Archived from the original on 2015-02-21. Retrieved 2013-09-17.
  14. PubChem. "Methaqualone". pubchem.ncbi.nlm.nih.gov. Retrieved 2021-05-19.
  15. Drug Enforcement Administration. "Established Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2022". Federal Register, the Daily Register of the United States Government.
  16. "The Meth Epidemic – Haislip discusses parallels to current Methamphetamine epidemic". Frontline. Boston: WGBH Educational Foundation.
  17. Ferns S (25 October 2007). "Lecture: Gene Haislip : The Chemical Connection: A Historical Perspective on Chemical Control" (PDF). Drug Enforcement Administration Museum Lecture Series. Arlington, Virginia. Archived from the original (PDF) on 31 March 2014.
  18. Piccini S (Spring 2010). "Drug Warrior: The DEA's Gene Haislip '60, B.C.L. '63 Battled Worldwide Against the Illegal Drug Trade – and Scored a Rare Victory" (PDF). William & Mary Alumni Magazine. College of William & Mary.
  19. "Mandrax". DrugAware. Reality Media. 2003. Retrieved 2009-08-13.
  20. McCarthy G, Myers B, Siegfried N (April 2005). "Treatment for methaqualone dependence in adults". The Cochrane Database of Systematic Reviews (2): CD004146. doi:10.1002/14651858.CD004146.pub2. PMID 15846700.
  21. "Project Coast: Apartheid's Chemical and Biological Warfare Programme" (PDF). Geneva, Switzerland: United Nations Institute for Disarmament Research (UNIDIR).

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