Methaqualone

Methaqualone
Systematic (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
Clinical data
Pregnancy
category
  • US: D (Evidence of risk)
Legal status
Identifiers
CAS Number 72-44-6 YesY
ATC code N05CM01
PubChem CID 6292
DrugBank DB04833 YesY
ChemSpider 6055 YesY
UNII 7ZKH8MQW6T YesY
KEGG D00557 YesY
ChEMBL CHEMBL282052 YesY
Chemical data
Formula C16H14N2O
Molar mass 250.30 g/mol
Physical data
Melting point 113 °C (235 °F)
  (verify)

Methaqualone, sold under the brand name Quaalude (\ˈkwā-ˌlüd\),[lower-alpha 1] in the US and Mandrax in the UK and South Africa, is a sedative and hypnotic medication. It is a member of the quinazolinone class.

The sedative–hypnotic activity of methaqualone was first noted by researchers in the 1950s. In 1962, methaqualone was patented in the US by Wallace and Tiernan.[2] Its use peaked in the early 1970s as a hypnotic, for the treatment of insomnia, and as a sedative and muscle relaxant.

Uses

Medical

Methaqualone is a depressant that increases the activity of the GABA receptors in the brain and nervous system. When GABA activity is increased, blood pressure drops and the breathing and pulse rates slow, leading to a state of deep relaxation. These properties explain why methaqualone was originally mainly prescribed for insomnia.[3]

Methaqualone peaks in the bloodstream within several hours, with a half-life of 20–60 hours. Regular users build up a physical tolerance, requiring larger doses for the same effect. Overdose can lead to nervous system shutdown, coma and death.[4]

Methaqualone is not recommended for use while pregnant and is in pregnancy category D.[5] In Canada, methaqualone is listed in Schedule III of the Controlled Drugs and Substances Act and requires a prescription.[6][7] Methaqualone is banned in India.[8]

Recreational

Methaqualone became increasingly popular as a recreational drug in the late 1960s and 1970s, known variously as ludes or sopers (also soaps) in the U.S. and mandrakes and mandies in the UK, Australia and South Africa.

The drug was often used by hippies and by people who went dancing at glam rock clubs in the 1970s and at discos. (One slang term for Quaalude was disco biscuits.) In the mid-1970s, there were bars in Manhattan called juice bars that only served non-alcoholic drinks that catered to people who liked to dance on methaqualone.[9]

Smoking methaqualone, either by itself or as an adulterant added to various legal and illegal smoking mixtures, gained popularity in the US for a few years during the mid-1970s. Because the various binders and inert ingredients that were contained in the pill form were toxic when smoked, this practice was roundly decried by the medical community as a serious health risk. Smoking methaqualone pills can lead to emphysema and other chronic lung disorders, most notably talcosis.

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 1982 and made a Schedule I drug in 1984. It has a DEA ACSCN of 2565 and in 2013 the aggregate annual manufacturing quota for the US was 10 grams. Mention of its possible use in some types of cancer and AIDS 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, and zero manufacturing quota.

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 says, "eliminated the problem".[10][11][12]

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 714s, "Lemmons", or "Lemmon 7s". 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 illegal manufacture of methaqualone all through the 1980s, continuing the use of the "714" stamp, until their popularity waned in the early 1990s. Purported methaqualone is in a significant minority of cases found to be inert, or contain diphenhydramine or benzodiazepines.

Methaqualone is one of the most commonly used recreational drugs in South Africa.[13][14] It is also popular elsewhere in Africa and in India.[14] Commonly known as Mandrax, M-pills, buttons, or smarties, a mixture of crushed mandrax and cannabis is smoked, usually through a smoking pipe made from the neck of a broken bottle.

Overdose

An overdose can cause 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 one tablet adult dose of Quaalude was 300 mg when made by Lemmon. A dose of 8000 mg is lethal. However, a dose as little as 2000 mg could also be lethal, especially if taken with an alcoholic beverage.[15]

Drug testing

Urine drug test of gas-liquid chromatography (GLC) confirmation up to 90 hours after the last intake is a practical way of detecting methaqualone use.[16]

To avoid a false positive Substance Abuse and Mental Health Services Administration (SAMHSA) determined the initial cut off level of 300 ng/ml for forensic and workplace drug testing of methaqualone. Only after testing at over 200 ng/ml is a person be considered positive, and possibly subject to penalties or workplace disciplinary action.[17] As reported by Quest Diagnostics in 2011, methaqualone had a 0% positive drug testing rate in the US, making it one of the least used recreational drugs in that year.[18]

Information provided by government, industrial, and academic sources most notably quoted in the textbook "Illegal Drugs" (Gahlinger, 2001) and some more in depth media reports list diphenhydramine and ostensibly other ethanolamine antihistamines as a potential source of methaqualone false-positives on immunoassay drug tests. Confirmation by low pressure vapour phase chromatography combined with mass spectrometry (GC/MS) should clear up the matter. Whether quinine and its relatives also have the potential to cause false positives is not known.

History

Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Hussain Zaheer, for use as an antimalarial drug.[15][19][20] 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, by Roussel Laboratories (now part of Sanofi-Aventis). In 1972, it was the sixth-bestselling sedative in the US,[21] 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" shared a stylistic reference to another drug marketed by the firm, Maalox, and was a portmanteau of the phrase "quiet interlude".[22]

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."[15]

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.[15]

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 and recreational use.[23]

The 2013 film The Wolf of Wall Street included a depiction of Quaalude intoxication (and driving under the influence) by Leonardo DiCaprio's character. Later, headlines were focused on Quaaludes after a deposition became public where Bill Cosby admitted under oath that he had given the drug to women whom he wanted to have sex with.[24]

As mentioned above, methaqualone is a common recreational and self-medication drug in South Africa and other of the former Frontline States, including Mozambique, Angola, Zambia and Zimbabwe. Some percentage of this consumption, as well as on the European and Near East clandestine drug markets, was/is in all probability sourced from the massive cache of powder and tabletted methaqualone produced under the aegis of the apartheid-era South African government's Project Coast in a segment thereof directed by Dr Wouter Basson (whose "Brownies" are capsules of pure MDMA in doses of up to 135 mg), who at one point was held by police in Croatia carrying $40m in Vatican bearer bonds when attempting to purchase 500 kilos of methaqualone. The methaqualone and MDMA, along with cocaine and other empathogens and aphrodisiacs as well as muscle relaxants and incapacitating anticholinergic deliriants were considered for non-lethal riot-control use. The entire drug cache disappeared into the underground in the final days of the National Party's tenure in office. The total methaqualone cache may have approached a metric ton.[25]

North, Central, and South American clandestine drug markets typically source the drug from industrial-scale illegal drug labs in Mexico, Colombia, Belize, Peru and elsewhere. Smaller labs occasionally are uncovered in the United States and Canada and the final percentage of methaqualone as well as mecloqualone, other chemical relatives, other congeners, and unreacted precursors form a chemical profile which can be used as a fingerprint to identify the likely origin of batches of the drug just as such things as morphine content and its relation to heroin content and presence of codeine, acetylcodeine, noscapine, papaverine, and other opium components form a chemical fingerprint for batches of heroin.[26]

Methaqualone is also a minor product of drug labs in Lebanon's Biqa Valley (also a supplier to African markets) and in all likelihood is produced for fundraising purposes by some combatants in the current Syrian Civil War, as is the case with heroin, opium, morphine, fentanyl analogues, Captagon, first generation amphetamines, cannabis, hashish and others. The government of the Democratic People's Republic of North Korea is a well-known industrial-scale producer of drugs such as dextromethamphetamine (Ice, Shabu, etc.) and other sympathomimetic stimulants for export to Asian and Australian clandestine drug markets and may supply some amount of methaqualone as well.[27] [28]

See also

Notes

  1. ↑ Pronounced /ˈkweɪluːd/ and sometimes stylized Quāālude[1]

References

  1. ↑ Rile, Karen (1983). Winter Music (First ed.). Boston and Toronto: Little, Brown and Company. pp. 41, 59. ISBN 0-316-74657-6.
  2. ↑ US Patent 3135659 – Hydroxy and Alkoxy Aryl Quinazolones
  3. ↑ "methaqualone reference". Enotes.
  4. ↑ "recreational drugs tranquilizers". drug library eu.
  5. ↑ Drug Safety. "Methaqualone in Pregnancy and Breastfeeding". Retrieved 15 August 2012.
  6. ↑ "Search National Drug Schedule".
  7. ↑ "Schedule III, Controlled Drugs and Substances Act". Her Majesty in Right of Canada. Retrieved 29 November 2014.
  8. ↑ "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Retrieved 2013-09-17.
  9. ↑ Lawrence Young (31 January 2010). "METHAQUALONE". Drug Text. International Substance Use Library. Retrieved 27 July 2012.
  10. ↑ "The Meth Epidemic – Haislip discusses parallels to current Methamphetamine epidemic".
  11. ↑ Ferns, Sean, "Lecture: Gene Haislip : The Chemical Connection: A Historical Perspective on Chemical Control", Drug Enforcement Administration Museum Lecture Series, Arlington, Virginia, October 25, 2007
  12. ↑ Piccini, Sara, "DRUG WARRIOR: THE DEA’S GENE HAISLIP ’60, B.C.L. ’63 BATTLED WORLDWIDE AGAINST THE ILLEGAL DRUG TRADE – AND SCORED A RARE VICTORY", William & Mary Alumni Magazine, The College of William & Mary, Spring 2010
  13. ↑ "Mandrax". DrugAware. Reality Media. 2003. Retrieved 2009-08-13.
  14. 1 2 "Treatment for methaqualone dependence in adults". Reviews (2): CD004146. 2005. doi:10.1002/14651858.CD004146.pub2. PMID 15846700.
  15. 1 2 3 4 Linder, Lee (28 May 1981). "Quaalude manufacturer: Image hurt by street use". Lawrence Journal-World. Associated Press. p. 6. Retrieved 16 August 2013. Eckman/Fisher
  16. ↑ "methaqualone drug testing". National Institute of Health.
  17. ↑ "methaqualone drug testing". Testcountry.
  18. ↑ "workplace drug test positive rates". quest diagnostics.
  19. ↑ van Zyl, Etienne F. (2001). "A survey of reported synthesis of methaqualone and some positional and structural isomers". Forensic Science International 122 (2–3): 142–149. doi:10.1016/S0379-0738(01)00484-4.
  20. ↑ Potential Analgesics. Part I. Synthesis of substituted 4-quinazolones, I. K. Kacker and S. H. Zaheer, J. Ind. Chem. Soc. 28 (1951), pp. 344–346.
  21. ↑ GC/MS Assays for Abused Drugs in Body fluids, p. 39
  22. ↑ "Dividends: Dropping the Last 'Lude". Time. 28 November 1983. Retrieved 16 August 2013.
  23. ↑ Silverstein, Shel. "Quaaludes Again". Captain Wayne's Mad Music.com.
  24. ↑ Harry Low and Tom Heyden (9 July 2015) The rise and fall of Quaaludes BBC News Magazine. Accessed 9 July 2015.
  25. ↑ Levenda, pp 302-303
  26. ↑ NCOCTL Bulletin Volume XXV, No 2, pp 3 sidebar "Blast From The Past"
  27. ↑ NCOCTL Bulletin Volume XXV, No 2, pp 3 sidebar "Blast From The Past"
  28. ↑ Ibid, pp 8, "Inside Syria"

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