 | |
| Clinical data | |
|---|---|
| Pronunciation | /mɛθəˈkweɪloʊn/ |
| Trade names | Quaalude, Sopor, Mandrax |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | 70–80% |
| Eliminationhalf-life | Biphasic (10–40; 20–60 hours) |
| Identifiers | |
| |
| CAS Number |
|
| PubChemCID | |
| DrugBank |
|
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.710 |
| Chemical and physical data | |
| Formula | C16H14N2O |
| Molar mass | 250.301 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 113 °C (235 °F) |
| |
| |
| (verify) | |
Methaqualone is asedative-hypnotic medication that was widely prescribed during the mid-20th century. It was marketed under various brand names, includingQuaalude (/ˈkweɪluːd/KWAY-lood) andSopor, typically containing 300 mg of methaqualone per tablet. Acombination drug known asMandrax was sold primarily in Europe, containing 250 mg of methaqualone and 20 mg ofdiphenhydramine in a single tablet.
Methaqualone belongs to thequinazolinone class of compounds. Its commercial production was discontinued in many countries during the mid-1980s due to widespread misuse, addiction, and associated public health concerns.
Methaqualone'ssedative-hypnotic properties were first identified in 1955. It gained popularity during the 1960s and 1970s for the treatment ofinsomnia, and as a generalsedative andmuscle relaxant. However, due to its abuse potential, it was eventually withdrawn from medical use.
The drug was classified aspregnancy category D, meaning there was evidence of risk to thehuman fetus, and it was not recommended during pregnancy.[2]
Like otherGABAergic substances, prolonged use of methaqualone can lead todrug tolerance,physical dependence, andwithdrawal symptoms upon cessation.[3]
Anoverdose of methaqualone can lead tocoma anddeath.[4]Additional effects aredelirium,convulsions,hypertonia,hyperreflexia,vomiting,kidney failure, and death throughcardiac orrespiratory arrest. Methaqualone overdose resemblesbarbituratepoisoning, 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 analcoholic beverage.[5]
Methaqualone acts primarily as a sedative, reducinganxiety and inducing sleep. It binds toGABAA receptors, where it functions as apositive allosteric modulator at many receptor subtypes, enhancing the inhibitory effects of the neurotransmitterGABA. It shows negligible affinity for a wide array of other potential targets, including other receptors andneurotransmitter transporters.[6] This action is similar to that ofbenzodiazepines likediazepam.
Unlike most benzodiazepines, however, methaqualone may also act as anegative allosteric modulator at certain GABAA receptor subtypes, producing excitatory effects in neurons expressing those receptors. As such, methaqualone is considered a mixed GABAA receptor modulator.[6]
The binding site for methaqualone on the GABAA receptor complex is distinct from those of benzodiazepines,barbiturates, andneurosteroids, though it may partially overlap with theetomidate binding site.[6]
Methaqualone reachespeak plasma concentrations within a few hours of administration. Itselimination half-life ranges between 20 and 60 hours, contributing to its sedative effects and potential for accumulation with repeated dosing.
Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker andSyed Husain Zaheer, who were conducting research on finding newantimalarial medications.[5][7][8] In 1962, methaqualone was patented in the United States byWallace and Tiernan.[9] 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 ofSanofi S.A.). In 1972, it was the sixth-bestselling sedative in the US,[10] where it was legal under thebrand name Quaalude.
Quaalude in the United States was originally manufactured in 1965 by the pharmaceutical firmWilliam H. Rorer, Inc., based inFort Washington, Pennsylvania. The drug name "Quaalude" is aportmanteau, combining the words "quiet interlude" and shared a stylistic reference to another drug marketed by the firm,Maalox.[11]
In 1978, Rorer sold the rights to manufacture Quaalude to the Lemmon Company ofSellersville, 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 ofPfizer, before the drug was discontinued in the United States in 1985, mainly due to its psychological addictiveness, widespread abuse, and illegal recreational use.[12]
A 2024 Hungarian investigative documentary reported on large-scale production and sales of the drug by theHungarian People's Republic to the United States in the 1970s and 1980s. It asserts that a Hungarianstate-owned company utilized connections toColombian drug cartels to facilitate the sale of extraordinary amounts to the United States.[13][14]
Methaqualone became increasingly popular as arecreational drug andclub drug in the late 1960s and 1970s, known variously as "ludes" or "disco biscuits"[15] due to its widespread use during the popularity ofdisco 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 afree base and as a salt (hydrochloride).
Methaqualone was sold under the brand name Quaalude (sometimes stylized "Quāālude" in theUnited States andCanada),[16] and Mandrax in theUK,South Africa, andAustralia.
Methaqualone was initially placed in Schedule I as defined by the UNConvention on Psychotropic Substances, but was moved to Schedule II in 1979.[17]
In Canada, methaqualone is listed in Schedule III of theControlled Drugs and Substances Act and requires a prescription, but it is no longer manufactured. Methaqualone is banned in India.[18]
In the United States it was withdrawn from the market in 1983 and made a Schedule I drug in 1984.[19]
Methaqualone became increasingly popular as a recreational drug in the late 1960s and 1970s, known variously as "ludes" or "sopers" and "soaps" (sopor is aLatin word for sleep) in the United States and "mandrakes" and "mandies" in the UK, Australia and New Zealand.
The drug was more tightly regulated in Britain under theMisuse 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 aSchedule I drug in 1984. It has a DEAACSCN of 2565 and in 2022 the aggregate annual manufacturing quota for the United States was 60[20] 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 analoguemecloqualone (also a result of some incomplete clandestine syntheses) to Schedule I as ACSCN 2572, with a manufacturing quota of 30 g.[20]
Gene Haislip, the former head of the Chemical Control Division of the Drug Enforcement Administration (DEA), told the PBS documentary programFrontline, "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".[21][22] Methaqualone was manufactured in the United States under the name Quaalude by the pharmaceutical firmsRorer 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 inMexico 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 inSouth 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".[23][24] It is popular elsewhere in Africa and in India.[24]
Illegal efforts to weaponize methaqualone have occurred. During the 1980s, theapartheid regime in South Africa ordered the covert manufacture of a large amount of methaqualone at thefront companyDelta G Scientific Company, as part of a secretchemical weapons program known asProject Coast.[25] Methaqualone was given the codenameMosRefCat (Mossgas Refinery Catalyst). Details of this activity came to light during the 1998 hearings of the post-apartheidTruth and Reconciliation Commission.
ActorBill Cosby admitted in a 2015 civil deposition to giving methaqualone to women beforeallegedly sexually assaulting them.[26][27] Film directorRoman Polanski was convicted in 1977 of sexually assaulting a 13-year-old girl after giving her alcohol and methaqualone.[28]
Quaaludes are mentioned in the 1983 filmScarface, when Al Pacino's character Tony Montana says, "Another quaalude... she'll love me again." Small white pills referred to as "ludes" appear along with several other illicit drugs in the 1983 comedy-dramaThe Big Chill.[29] Quaaludes are also referenced extensively in the 2013 filmThe Wolf of Wall Street.[30] They are briefly mentioned in the movieDinner in America as the reason behind the behavior of one of the characters.Almost Famous is another movie where the drug appears, as "Penny Lane", played byKate Hudson, is shown to have taken quaaludes during a scene in which she is drugged.[31][32]
Parodyglam rocker "Quay Lewd", one of the costumed performance personae used byTubes singerFee Waybill, was named after the drug. Many songs also refer to quaaludes, including the following:David Bowie's "Time" ("Time, in quaaludes and red wine"), "Rebel Rebel" ("You got your cue line/And a handful of 'ludes"), when signing "All The Young Dudes" on stage Bowie would often use the line ("All The Young Dudes, carry the ludes");Lou Reed's song "The Last Shot" ("Shot a vein in my neck and I coughed up a Quaalude"); "Cosmic Doo Doo" by the Americancountry music singer-songwriterBlaze Foley ("Got some quaaludes in their purse"); "That Smell" byLynyrd Skynyrd ("Can't speak a word when you're full of 'ludes"); "Flakes" byFrank Zappa ("Wanna buy some mandies, Bob?"); "Straight Edge" byMinor Threat ("Laugh at the thought of eating ludes"); "Kind of Girl" byFrench Montana ("That high got me feelin' like the Quaaludes fromWolf of Wall Street"); and "Nights" byFrank Ocean ("This feel like a Quaalude")
Season 18 ofLaw & Order: Special Victims Unit addresses Quaalude administration as adate rape drug in episode 9, "Decline and Fall", which aired January 18, 2017.[33][34] InTrue Detective season 1,Rust Cohle's use of Quaaludes is briefly mentioned in several episodes.[35]
It is also used by Patrick Melrose inEdward St Aubyn's 1992 novelBad News.[citation needed]
In the 2024 filmMaria,Maria Callas, played byAngelina Jolie, stuffs Mandrax into the pockets of her coats and bags so that she'll be able to escape detection by her butler/guardian Ferruccio (Pierfrancesco Favino).
The 2000 novelHouse of Leaves byMark Z. Danielewski features the supporting character named Lude, referencing Quaaludes.
Eckman/Fisher
| International | |
|---|---|
| National | |
| Other | |
