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56-481: Methaqualone is a hypnotic sedative . It was sold under the brand names Quaalude ( / ˈ k w eɪ l uː d / 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

112-486: A pharmacist in Pennsylvania . The business remained small, primarily selling pain relievers until 1949 when it introduced Maalox . Maalox was developed in collaboration between William H. Rorer, Inc. and a medical doctor and researcher specializing in gastrointestinal issues, Alison Howe Price from Philadelphia . The collaboration came about after World War II when Claude Newhart, a salesman and pharmacist for

168-633: A Schedule I drug in 1984. 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

224-551: A drugstore in Philadelphia , Martin H. Rehfuss, who happened to be chief of medicine at Thomas Jefferson Hospital. It was Mr. Rehfuss who introduced Mr. Newhart to Dr. Price. It wasn’t long before Mr. Newhart convinced Price to become a consultant for the Fort Washington, Pennsylvania based Willam H. Rorer, Inc. And it so happened that the first product the partnership produced was Maalox . It eventually would become

280-545: A first-line long-term treatment of insomnia. However, the UK National Institute for Health and Clinical Excellence (NICE) did not find any convincing evidence in favor of Z-drugs. A NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing

336-522: A large amount of methaqualone at the front company Delta G Scientific Company , as part of a secret chemical weapons program known as Project Coast . 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 . Actor Bill Cosby admitted in a 2015 civil deposition to giving methaqualone to women before allegedly sexually assaulting them . Film director Roman Polanski

392-456: 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 . Methaqualone primarily acts as a sedative, relieving anxiety and promoting sleep. Methaqualone binds to GABA-A receptors , and it shows negligible affinity for

448-522: A molecular level. Examples include zopiclone (Imovane, Zimovane), eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Stilnox, Stilnoct). Since the generic names of all drugs of this type start with Z, they are often referred to as Z-drugs. Research on nonbenzodiazepines is new and conflicting. A review by a team of researchers suggests the use of these drugs for people that have trouble falling asleep (but not staying asleep), as next-day impairments were minimal. The team noted that

504-416: A much lower degree than the first ones. This results in their primarily affecting peripheral histamine receptors, and therefore having a much lower sedative effect. High doses can still induce the central nervous system effect of drowsiness. Some antidepressants have sedating effects. Examples include: While some of these drugs are frequently prescribed for insomnia, such use is not recommended unless

560-505: A negative allosteric modulator at a few GABA-A receptor subtypes, which tends to cause an excitatory response in neurons expressing those receptors. Because methaqualone can be either excitatory or inhibitory depending on the subunit composition of the GABA-A receptor, it can be characterized as a mixed GABA-A receptor modulator. The methaqualone binding site is distinct from the benzodiazepine , barbiturate , and neurosteroid binding sites on

616-624: A side effect that are occasionally used for insomnia: A major systematic review and network meta-analysis of medications for the treatment of insomnia was published in 2022. It found a wide range of effect sizes ( standardized mean difference (SMD)) in terms of efficacy for insomnia. The assessed medications included benzodiazepines (e.g., temazepam , triazolam , many others) (SMDs 0.58 to 0.83), Z-drugs ( eszopiclone , zaleplon , zolpidem , zopiclone ) (SMDs 0.03 to 0.63), sedative antidepressants and antihistamines ( doxepin , doxylamine , trazodone , trimipramine ) (SMDs 0.30 to 0.55),

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672-433: A wide array of other potential targets, including other receptors and neurotransmitter transporters . Methaqualone is a positive allosteric modulator at many subtypes of GABA-A receptor, similar to classical benzodiazepines such as diazepam . GABA-A receptors are inhibitory, so methaqualone tends to inhibit action potentials, similar to GABA itself or other GABA-A agonists. Unlike most benzodiazepines, methaqualone acts as

728-473: A withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation. The list of benzodiazepines approved for the treatment of insomnia is fairly similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia can vary distinctly between countries. Longer-acting benzodiazepines such as nitrazepam and diazepam have residual effects that may persist into

784-892: Is also used by Patrick Melrose in Edward St Aubyn 's 1992 novel Bad News . Hypnotic This group of drugs is related to sedatives . Whereas the term sedative describes drugs that serve to calm or relieve anxiety , the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness ), they are often referred to collectively as sedative–hypnotic drugs. Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. Many hypnotic drugs are habit-forming and—due to many factors known to disturb

840-689: Is believed to be positive allosteric modulation of GABA A receptors. Examples include amobarbital , pentobarbital , phenobarbital , secobarbital , and sodium thiopental . Quinazolinones are also a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core. Their use has also been proposed in the treatment of cancer . Examples of quinazolinones include cloroqualone , diproqualone , etaqualone (Aolan, Athinazone, Ethinazone), mebroqualone , Afloqualone (Arofuto), mecloqualone (Nubarene, Casfen), and methaqualone (Quaalude). Benzodiazepines can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks

896-453: Is not recommended due to the risk of dependence. It is preferred that benzodiazepines be taken intermittently—and at the lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging the sleep time, and, in general, reducing wakefulness. Like alcohol , benzodiazepines are commonly used to treat insomnia in the short-term (both prescribed and self-medicated), but worsen sleep in

952-644: 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". It is popular elsewhere in Africa and in India. Illegal efforts to weaponize methaqualone have occurred. During the 1980s, the apartheid regime in South Africa ordered the covert manufacture of

1008-437: Is primarily at GABA A receptors . Nonbenzodiazepines are a class of psychoactive drugs that are very "benzodiazepine-like" in nature. Nonbenzodiazepine pharmacodynamics are almost entirely the same as benzodiazepine drugs, and therefore entail similar benefits, side-effects and risks. Nonbenzodiazepines, however, have dissimilar or entirely different chemical structures, and therefore are unrelated to benzodiazepines on

1064-556: The Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D) . The use of these medications can further impede cognitive function for people with dementia, who are also more sensitive to side effects of medications. William H. Rorer, Inc. William H. Rorer, Inc was an American multinational pharmaceutical company headquartered in Fort Washington, Pennsylvania . It

1120-468: The antipsychotic quetiapine (SMD 0.07), orexin receptor antagonists ( daridorexant , lemborexant , seltorexant , suvorexant ) (SMDs 0.23 to 0.44), and melatonin receptor agonists ( melatonin , ramelteon ) (SMDs 0.00 to 0.13). The certainty of evidence varied and ranged from high to very low depending on the medication. Certain medications often used as hypnotics, including the antihistamines diphenhydramine , hydroxyzine , and promethazine and

1176-617: The over-the-counter allergy and antiemetic medications doxylamine and diphenhydramine . Off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe (as in patients with a history of substance abuse ). Barbiturates are drugs that act as central nervous system depressants , and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia . They are also effective as anxiolytics , hypnotics, and anticonvulsalgesic effects; however, these effects are somewhat weak, preventing barbiturates from being used in surgery in

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1232-477: The 1970s, quinazolinones and benzodiazepines were introduced as safer alternatives to replace barbiturates; by the late 1970s, benzodiazepines emerged as the safer drug. Benzodiazepines are not without their drawbacks; substance dependence is possible, and deaths from overdoses sometimes occur, especially in combination with alcohol and/or other depressants . Questions have been raised as to whether they disturb sleep architecture. Nonbenzodiazepines are

1288-511: The DEA was able to halt production and, Haislip said, "eliminated the problem". 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

1344-455: The GABA-A receptor complex, and it may partially overlap with the etomidate binding site. Methaqualone peaks in the bloodstream within several hours, with a half-life of 20–60 hours. 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 . In 1962, methaqualone was patented in

1400-599: 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." 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

1456-513: The USA. Early classes of drugs, such as barbiturates , have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable—unless used to treat night terrors or sleepwalking . Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairments , and a meta-analysis found that the risks generally outweigh any marginal benefits of hypnotics in

1512-406: The United States by Wallace and Tiernan . 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, where it

1568-545: The absence of other analgesics. They have dependence liability, both physical and psychological . Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – such as in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose . However, barbiturates are still used in general anesthesia, for epilepsy , and for assisted suicide . Barbiturates are derivatives of barbituric acid . The principal mechanism of action of barbiturates

1624-606: 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. 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. A 2024 Hungarian investigative documentary reported on large-scale production and sales of

1680-430: The antidepressants amitriptyline and mirtazapine , were not included in analyses due to insufficient data. The use of sedative medications in older people generally should be avoided. These medications are associated with poorer health outcomes, including cognitive decline , and bone fractures. Therefore, sedatives and hypnotics should be avoided in people with dementia, according to the clinical guidelines known as

1736-491: The company had an idea that he thought might change the company’s fortunes. According to the Rorer family, he suggested that instead of selling pain relievers that the company didn’t manufacture, they should create their own products. Gerald Rorer, president of Rorer and son of the founder, told Mr. Newhart to “go and find something.” Mr. Newhart took up the challenge and contacted an old acquaintance from his student days employed at

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1792-519: The drug by the Hungarian People's Republic to the United States in the 1970s and 1980s. It asserts that a Hungarian state-owned company utilized connections to Colombian drug cartels to facilitate the sale of extraordinary amounts to the United States. 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

1848-489: The drugmaker's sales. In order to diversify, Rorer merged with AmChem in 1968, an agricultural herbicide producer to form Rorer-AmChem. The merger did not turn out to be profitable and in 1977 Rorer sold AmChem to Union Carbide . By the late 1980s, the pharmaceutical industry had experienced significant mergers, making it very difficult for Rorer to compete. In 1990 the company merged with Rhone-Poulenc SA, France's largest pharmaceuticals' company, for 3.2 billion dollars. At

1904-413: The elderly. A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep. Falling outside the above-mentioned categories,

1960-584: The human sleep pattern—a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene , the avoidance of caffeine and alcohol or other stimulating substances, or behavioral interventions such as cognitive behavioral therapy for insomnia (CBT-I), before prescribing medication for sleep. When prescribed, hypnotic medication should be used for the shortest period of time necessary. Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines , while 10.8% are taking benzodiazepines , as of 2010, in

2016-486: The hypnotic based on cost and the patient's preference. Older adults should not use benzodiazepines to treat insomnia—unless other treatments have failed to be effective. When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence which shows twice the incidence of traffic collisions among driving patients, as well as falls and hip fracture for all older patients. Their mechanism of action

2072-577: The insomnia is due to an underlying mental health condition treatable by antipsychotics as the risks frequently outweigh the benefits. Some of the more serious adverse effects have been observed to occur at the low doses used for this off-label prescribing, such as dyslipidemia and neutropenia , and a recent network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine had not demonstrated any short-term benefits in sleep quality. Examples of antipsychotics with sedation as

2128-484: The last half of the 20th century. Treatment for insomnia in psychiatry dates back to 1869, when chloral hydrate was first used as a soporific. Barbiturates emerged as the first class of drugs in the early 1900s, after which chemical substitution allowed derivative compounds. Although they were the best drug family at the time (with less toxicity and fewer side effects), they were dangerous in overdose and tended to cause physical and psychological dependence. During

2184-481: 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

2240-465: The long-term. While benzodiazepines can put people to sleep (i.e., inhibit NREM stage 1 and 2 sleep), while asleep, the drugs disrupt sleep architecture by decreasing sleep time, delaying time to REM sleep, and decreasing deep slow-wave sleep (the most restorative part of sleep for both energy and mood). Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomnia , and reduced slow-wave sleep and

2296-617: 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. 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,

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2352-711: The most recent development (1990s–present). Although it is clear that they are less toxic than barbiturates, their predecessors, comparative efficacy over benzodiazepines have not been established. Such efficacy is hard to determine without longitudinal studies . However, some psychiatrists recommend these drugs, citing research suggesting they are equally potent with less potential for abuse. Other sleep remedies that may be considered "sedative–hypnotics" exist; psychiatrists will sometimes prescribe medicines off-label if they have sedating effects. Examples of these include mirtazapine (an antidepressant), clonidine (an older antihypertensive drug ), quetiapine (an antipsychotic), and

2408-428: The neurohormone melatonin and its analogues (such as ramelteon ) serve a hypnotic function. Hypnotica was a class of somniferous drugs and substances tested in medicine of the 1890s and later. These include Urethan , Acetal , Methylal , Sulfonal , Paraldehyde , Amylenhydrate , Hypnon , Chloralurethan and Ohloralamid or Chloralimid . Research about using medications to treat insomnia evolved throughout

2464-559: The next day and are, in general, not recommended. It is not clear as to whether the new nonbenzodiazepine hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar. According to the US Agency for Healthcare Research and Quality , indirect comparison indicates that side-effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines. Some experts suggest using nonbenzodiazepines preferentially as

2520-614: 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). It was sold under the brand name Quaalude (sometimes stylized "Quāālude" in the United States and Canada ), and Mandrax in the UK , South Africa , and Australia . Methaqualone

2576-649: The safety of these drugs had been established, but called for more research into their long-term effectiveness in treating insomnia. Other evidence suggests that tolerance to nonbenzodiazepines may be slower to develop than with benzodiazepines . A different team was more skeptical, finding little benefit over benzodiazepines. Melatonin , the hormone produced in the pineal gland in the brain and secreted in dim light and darkness, among its other functions, promotes sleep in diurnal mammals. Ramelteon and tasimelteon are synthetic analogues of melatonin which are also used for sleep-related indications. In common use,

2632-411: The term antihistamine refers only to compounds that inhibit action at the H 1 receptor (and not H 2 , etc.). Clinically, H 1 antagonists are used to treat certain allergies . Sedation is a common side-effect, and some H 1 antagonists, such as diphenhydramine (Benadryl) and doxylamine , are also used to treat insomnia. Second-generation antihistamines cross the blood–brain barrier to

2688-492: The thought of eating ludes"); and "Kind of Girl" by French Montana ("That high got me feelin' like the Quaaludes from Wolf of Wall Street "). Season 18 of Law & Order: Special Victims Unit addresses Quaalude administration as a date rape drug in episode 9, "Decline and Fall", which aired January 18, 2017. In True Detective season 1 , Rust Cohle 's use of Quaaludes is briefly mentioned in several episodes. It

2744-416: The world's best selling antacid and forever change the company's fortunes. In 1965 the company introduced Quaalude (quiet interlude), similar in spelling to its top-selling antacid, Maalox, but it turned out to be far less successful for the company. The FDA withdrew Quaalude in 1984. Rorer's was headquartered in Fort Washington, Pennsylvania . For many years Maalox comprised a large proportion of

2800-457: Was convicted in 1977 of sexually assaulting a 13-year-old girl after giving her alcohol and methaqualone. Quaaludes are mentioned in the 1983 film Scarface , when Al Pacino's character Tony Montana says, "Another quaalude... she'll love me again." Quaaludes are also referenced extensively in the 2013 film The Wolf of Wall Street . Parody glam rocker "Quay Lewd", one of the costumed performance personae used by Tubes singer Fee Waybill ,

2856-415: Was founded in 1910 by William H. Rorer, a Pennsylvania pharmacist . The business operated as a small concern, primarily selling pain relievers manufactured elsewhere. It wasn't until after World War II that the company's fortunes forever changed with the introduction of Maalox which would become the world's best selling antacid. Willaim H. Rorer founded William H. Rorer, Inc. in 1910 while working as

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2912-848: Was halted in the mid-1980s due to widespread abuse and addictiveness. It is a member of the quinazolinone class. The sedative–hypnotic activity of methaqualone was recognized in 1955. Its use peaked in the early 1970s for the treatment of insomnia , and as a sedative and muscle relaxant . Methaqualone was not recommended for use while pregnant and is in pregnancy category D . Similar to other GABAergic agents, methaqualone will produce tolerance and physical dependence with extended periods of use. An overdose of methaqualone can lead to coma and death . Additional effects are delirium , convulsions , hypertonia , hyperreflexia , vomiting , kidney failure , and death through cardiac or respiratory arrest . Methaqualone overdose resembles barbiturate poisoning , but with increased motor difficulties and

2968-646: Was initially placed in Schedule I as defined by the UN Convention on Psychotropic Substances , but was moved to Schedule II in 1979. 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. In the United States it was withdrawn from the market in 1983 and made

3024-429: Was legal under the brand name Quaalude. Quaalude in the United States was originally manufactured in 1965 by the pharmaceutical firm William H. Rorer, Inc. , based in Fort Washington, Pennsylvania . 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 . In 1978, Rorer sold the rights to manufacture Quaalude to

3080-591: Was named after the drug. Many songs also refer to quaaludes, including the following: David Bowie 's " Time " ("Time, in quaaludes and red wine") and " Rebel Rebel " ("You got your cue line/And a handful of 'ludes"); "Cosmic Doo Doo" by the American country music singer-songwriter Blaze Foley ("Got some quaaludes in their purse"); " That Smell " by Lynyrd Skynyrd ("Can't speak a word when you're full of 'ludes"); " Flakes " by Frank Zappa ("(Wanna buy some mandies, Bob?)"); " Straight Edge " by Minor Threat ("Laugh at

3136-486: 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 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

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