{{short description, 5mg methamphetamine hydrochloride (Desoxyn) and 30mg pentobarbital sodium (Nembutal) Desbutal was a brand name drug by Abbott containing 5mg methamphetamine hydrochloride (Desoxyn) and 30mg pentobarbital sodium (Nembutal); a

substituted amphetamine Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

and a

barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...

combined within the same pill. Desbutal was

marketed Marketing is the process of exploring, creating, and delivering value to meet the needs of a target market in terms of goods and services; potentially including selection of a target audience; selection of certain attributes or themes to emph ...

as an

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

as well as a medication for the treatment of

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy bo ...

, and

alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...

, although it was commonly also prescribed off-label for miscellaneous ailments. It had a high abuse potential and is no longer manufactured.

Dosage forms

Desbutal was designed as round biphasic tablets, with the two

active ingredient An active ingredient is any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. T ...

s visibly partitioned between the two faces of the tablet to control their rates of dissolution and achieve a more preferable

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

profile. Each tablet featured a yellow half which contained an immediate-release formulation of pentobarbital sodium, and a blue half which contained a

sustained-release Modified-release dosage is a mechanism that (in contrast to immediate-release dose (biochemistry), dosage) delivers a drug with a delay after its route of administration, administration (delayed-release dosage) or for a prolonged period of time (e ...

formulation of methamphetamine hydrochloride (Desoxyn Gradumet). The three dosages of tablets that were manufactured included 5mg, 10mg, and 15mg of methamphetamine hydrochloride with 30mg, 60mg, and 90mg of pentobarbital sodium, respectively.

Abuse Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...

of Desbutal often involved physical separation of these two halves by sawing with a razor or fingernails, followed by the consumption of each active ingredient independently rather than concurrently. Typically abusers would ingest the blue half containing methamphetamine for stimulation and

wakefulness Wakefulness is a daily recurring Human brain, brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of ...

, followed by future ingestion of the yellow half containing pentobarbital as a

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

for counteracting stimulant-induced

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

whenever sleep was desired.

Overdose

A Desbutal

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

typically becomes life-threatening as a result of

acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

from pentobarbital poisoning, since the

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

median lethal dose (LD₅₀) of pentobarbital sodium is reached significantly sooner than the oral LD₅₀ of methamphetamine hydrochloride when consumed as dosage units with the mass ratio present in Desbutal.

Barbiturate overdose Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). Complica ...

is a

medical emergency A medical emergency is an acute injury or illness that poses an immediate risk to a person's life or long-term health, sometimes referred to as a situation risking "life or limb". These emergencies may require assistance from another, qualified p ...

which was treated with immediate

gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...

mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...

, and intermittent

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

bolus administration of multiple different drugs, since no selective barbiturate

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may inclu ...

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

s were clinically available as an

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

, and dosages were dependent on individual patient response. These drugs often included

picrotoxin Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Gree ...

amiphenazole Amiphenazole (Daptazile) is a respiratory stimulant traditionally used as an antidote for barbiturate or opiate overdose, usually in combination with bemegride, as well as poisoning from other sedative drugs and treatment of respiratory failure ...

(Daptazile), bemegride (Megimide), and methamphetamine sulfate (Methedrine) in dosages sometimes exceeding 250mg over the first 24 hour period of being admitted into an intensive care unit (ICU). While a quantitative relationship between the blood levels of barbiturate derivatives and the depression of the central nervous system (CNS) had become established by researchers in 1955, they also emphasized that the accurate correlation of these factors is complicated by the presence of tolerance to the drug, intercurrent disease and

senility Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affec ...

, as well as the concurrent administration of other noxious substances.

Regulations

Desbutal is no longer manufactured since withdrawal of its marketing approval by the Food and Drug Administration (FDA) in 1973 as part of a mass

recall Recall may refer to: * Recall (bugle call), a signal to stop * Recall (information retrieval), a statistical measure * ''ReCALL'' (journal), an academic journal about computer-assisted language learning * Recall (memory) * ''Recall'' (Overwatch ...

of all obesity

combination drug A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

s containing a

CNS stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

, often with a

CNS depressant A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...

. The recall also included all existing stocks of

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

amphetamines based on the FDA's contention that these products have such a great drug

abuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

that they cannot be used safely. Although the Bureau of Narcotics and Dangerous Drugs (BNDD) had already reduced the amphetamine aggregate production quota (APQ) for

pharmaceutical manufacturers The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate symptoms. ...

by approximately 90% throughout the prior two years, these combination drugs had rapidly grown in popularity throughout the two preceding decades. Many

were vigorously

competing Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indivi ...

for

market share Market share is the percentage of the total revenue or sales in a market that a company's business makes up. For example, if there are 50,000 units sold per year in a given industry, a company whose sales were 5,000 of those units would have a ...

s by continuously developing new combinations and dosage formulations, and at the time of the 1973 recall, the estimated annual distribution of these pills was equivalent to 480 million dosage units of

Obetrol Obetrol was the brand name of a drug combining several amphetamine salts indicated for the treatment of exogenous obesity. It was originally sold by the American company Obetrol Pharmaceuticals. Obetrol was a popular diet pill in America in the ...

10mg tablets.

Medical uses

The medical justification for these combination drugs was that the CNS stimulant elevates mood and suppresses appetite, while the CNS depressant mitigates many of the

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

s of the CNS stimulant without simultaneously reducing its therapeutic benefits. Some psychiatrists will attempt to duplicate this effect, albeit only partially, using stimulants in conjunction with benzodiazepines such as clonazepam in patients with certain forms of refractory depression where monoamine oxidase inhibitors such as nardil or parnate would be indicated, but lacking the dangers associated with that class of medication, as maois are extremely toxic in cases of overdose or deliberate or accidental ingestion of tyramine. This combination is regarded as extremely effective by patients and practitioners alike, and retains efficacy over time when used as directed, but both drugs do carry risks of abuse and dependency. Typically the CNS stimulant within these older combination drugs was

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and ...

, or methamphetamine as various single or mixed salts, and phenmetrazine hydrochloride (Preludin) was also marketed albeit less frequently. Typically the CNS depressant within these combination drugs was a single barbiturate salt, especially pentobarbital sodium and

sodium amobarbital Amobarbital (formerly known as amylobarbitone or sodium amytal as the soluble sodium salt) is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. ...

(Amytal), although

meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benz ...

(Miltown), a

minor tranquilizer An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

, and methaqualone hydrochloride (Quaalude), a non-barbiturate

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

were also sometimes used. Some less common combination drug formulations included a CNS stimulant combined with multiple

vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...

s and

minerals In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2 ...

, a

first generation antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

(

Eskatrol Eskatrol was an amphetamine weight loss agent which was removed by the U.S. Food and Drug Administration , Food and Drug Administration (FDA) in 1981 after its manufacturer, Smith, Kline & French , SmithKline & French (SKF), failed to prove the ...

was popular), or a

first generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of h ...

( Obocell-TF). Other formulations utilized amphetamines, barbiturates, and meprobamate for their ability to potentiate

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

by combining them with analgesics such as

phenacetin Phenacetin (acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn ...

and

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

References

External links