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Glutethimide

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Glutethimide

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Medically reviewed

Marina Burgos

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Glutethimide

Quick Facts

Property Description
Active ingredient Glutethimide
Form Tablet (oral)
Pharmacological class Sedative-Hypnotic
Common use Relief from insomnia symptoms
Origin Synthetic organic compound

Glutethimide: Definition, Class, and Origin

Glutethimide is a prescribed pharmaceutical agent categorized as a sedative-hypnotic drug intended to facilitate sleep onset. This medication is a synthetic organic compound belonging to the piperidinedione chemical class. Its active ingredient is Glutethimide itself, known chemically as C13H15NO2. This compound is clinically recognized for its potent depressant effects on the central nervous system.

It is specifically defined as a non-barbiturate hypnotic. This is a key differentiating factor, signifying that while the drug's clinical effects—such as rapid sleep induction—are functionally similar to those of older sleep aids, its core chemical structure is distinct, setting it apart from the barbiturate family. The drug's synthetic origin confirms its structure is a result of intentional chemical design.

Pharmacological Type and General Purpose

The drug is fundamentally categorized as a Central Nervous System (CNS) Depressant, which means its core action is to generally reduce the functional activity and excitability of the brain and spinal cord. Glutethimide achieves this effect by enhancing the effectiveness of the body's natural inhibitory neurotransmitter.

This classification as a CNS depressant leads directly to its general purpose. The medication is commonly used in scenarios requiring temporary support for severe difficulty in falling or staying asleep, serving as a powerful aid against sleep deprivation. The primary therapeutic purpose of this action is to provide high-level relief from the symptoms of insomnia, facilitating the onset of sleep through its strong sedative properties. Glutethimide is typically manufactured as a single-entity product designed for the oral route of administration in a tablet dosage form.

Regulatory References

  1. Glutethimide as a Non-Barbiturate Hypnotic

What side effects are possible with Glutethimide?

Possible side effects and safety information

The official regulatory safety characteristics of Glutethimide reflect its nature as a potent Central Nervous System (CNS) depressant with a high potential for abuse and dependence. This classification establishes the medicine as a controlled substance, indicating that chronic administration may result in the development of severe physical or psychological dependence.

Documented Adverse Reactions and Organ Systems

Adverse reactions documented in official regulatory documents are classified across several physiological systems. Effects on the Nervous System and Psychiatric domains may include residual sedation (hangover effect), headache, vertigo, and paradoxical excitation. Reactions affecting the Gastrointestinal System include gastric irritation, nausea, and diarrhea. Skin disorders are also documented, encompassing various forms of rash and, rarely, severe conditions like exfoliative dermatitis.

Serious Adverse Reactions and Safety Considerations

Clinically significant serious adverse reactions, which occur infrequently, affect multiple organ systems. The greatest risk to the patient is severe respiratory depression and the potential for coma in cases of acute intoxication. Other rare serious events include blood dyscrasias (e.g., aplastic anemia), peripheral neuropathy, and jaundice. A specific time-related pattern is documented for a metabolic effect: osteomalacia has been attributed to long-term use.

Safety notes require caution in specific populations, such as patients with closed-angle glaucoma, prostatic hypertrophy, or certain cardiac arrhythmias. Concomitant use with alcohol is documented to enhance the hypnotic effects, posing a significant safety consequence. The drug's ability to induce microsomal hepatic enzymes may also affect the metabolism of other co-administered medicines.

Overdose and Emergency Response

Official Manifestations of Overdose

Regulatory documentation describes Glutethimide overdosage as a severe event marked by profound Central Nervous System (CNS) depression. Documented clinical manifestations include continuing confusion, severe weakness, slurred speech, staggering, and a slowness or loss of reflexes. Muscle spasms, twitching, and convulsions (seizures) may also occur.

Overdose may rapidly progress to Severe Systemic Life-Threatening Outcomes. These include respiratory depression (shortness of breath or slow/troubled breathing) and severe hypotension (low blood pressure), which can lead to unconsciousness, coma, and potential death. Cyanosis, a bluish coloration of the skin, is also a reported sign.

When to Seek Immediate Medical Help

The official guidance mandates that if a Glutethimide overdose is suspected, emergency help must be sought at once. Management is focused on providing aggressive supportive treatment. This may require procedures such as the use of assisted ventilation to manage respiratory failure, and techniques like hemodialysis to aid in drug elimination. Priority for intensive care and monitoring is required for high-risk patients.

Population-Specific Considerations

Regulatory information notes that overdose is especially dangerous in children. Furthermore, elderly individuals are specifically identified as a high-risk group, with a greater potential for a fatal outcome, necessitating priority for intensive care and continuous observation.

Therapeutic Uses of Glutethimide

What Glutethimide Treats: Main Uses and Benefits

The therapeutic application of Glutethimide is focused on managing symptoms related to heightened physiological activity and central nervous system (CNS) arousal. It is generally considered relevant as a sedative and hypnotic agent.

The primary therapeutic domain is providing support for severe sleep onset and maintenance difficulties (insomnia), but it is also applied for supportive sedative relief in acute clinical situations, and in specialized contexts, is relevant for easing refractory motor symptoms like certain disabling action tremors. This wide scope means it is commonly used across conditions presenting with acute episodes and periods of heightened discomfort.

“This medication is applied in domains where additional symptomatic support is needed, assisting with easing pronounced symptoms.”

Glutethimide is applied across domains where symptomatic support is needed for patients experiencing profound difficulties in falling asleep and staying asleep. This use is targeted at alleviating the intense symptom clusters associated with chronic sleep deprivation, and may assist with maintaining functional stability by supporting continuous sleep. This application is particularly relevant when symptoms become temporarily overwhelming, providing supportive relief prior to procedures or for addressing treatment-resistant motor manifestations.

Quick Fact: Support for Sleep-Related Symptoms Glutethimide is commonly used to help with the symptomatic burden resulting from profound difficulties in initiating or maintaining sleep.

Eligibility and Restrictions for Use

Who Can and Cannot Use Glutethimide

The official regulatory profile for Glutethimide establishes clear rules on population eligibility, distinguishing between absolute prohibitions, conditional restrictions, and age-based limitations.

Population Status Condition/Group
Contraindicated Porphyria
Not Recommended Paediatric Use (Children)
Restricted Use Closed-angle glaucoma, Prostatic hypertrophy, Urinary tract obstruction, Certain cardiac arrhythmias
Eligible Adults

Glutethimide is absolutely contraindicated in patients diagnosed with porphyria, meaning use is strictly prohibited by regulatory authorities for this metabolic disorder. The medicine is generally intended for adults who are the standard eligible population; its use is formally not recommended in the paediatric population (children).

Furthermore, use is permitted only under conditions of great care for individuals with specific comorbidities due to the drug's properties. These restricted patient populations include those with closed-angle glaucoma, prostatic hypertrophy, urinary tract obstruction, or certain cardiac arrhythmias. The regulatory labeling requires this explicit caution in these specific circumstances. For physiological states like pregnancy and lactation, an explicit eligibility or restriction status is not formally documented in the primary authoritative regulatory summaries.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Glutethimide's official interaction profile is characterized by two primary mechanisms documented in regulatory sources: its effect on liver enzymes and its additive effect on the central nervous system.

Pharmacokinetic Interactions (Exposure Modification)

Glutethimide is documented as a potent inducer of liver microsomal enzymes, which includes the action of CYP2D6 enzyme induction. This activity can significantly alter the metabolism of co-administered medicines.

  • Coumarin Anticoagulants (e.g., Warfarin): Glutethimide enhances the metabolism of these agents, which formally results in lowered plasma concentrations of the anticoagulant.
  • Codeine: Due to enhanced metabolism via enzyme induction, co-administration can lead to a potentiated and prolonged analgesic effect.

Pharmacodynamic Interactions

Glutethimide exhibits additive effects with other agents that cause CNS depression.

  • CNS Depressants: Co-administration with other Central Nervous System Depressants—such as opioids, benzodiazepines, and tricyclic antidepressants—increases the risk and severity of additive CNS depression.

Drug–Substance Interactions

  • Alcohol (Ethanol): Co-ingestion with alcohol is officially documented to enhance the absorption of Glutethimide and significantly potentiate its hypnotic effects.

No mandatory administration timing rules or formal drug-drug combination contraindications are explicitly stated in available regulatory labeling.

Mechanism of Action

Glutethimide's primary mechanism involves the GABA A receptor complex, a critical target in the central nervous system ( CNS) that regulates neuronal inhibition.

Positive Allosteric Modulation of GABA A Receptors

This mechanism describes Glutethimide's role as a positive allosteric modulator that enhances the inhibitory effect of the GABA neurotransmitter. The drug binds to a specific allosteric site on the receptor, increasing the frequency of chloride ion ( Cl^-) channel openings triggered by GABA. This action facilitates the influx of negatively charged Cl^- ions into the postsynaptic neuron. The increased negative charge causes neuronal hyperpolarization, reducing the cell's excitability and resulting in altered neuronal signaling within the CNS.

Modulation of Hepatic Drug Metabolism (CYP Induction)

Glutethimide also functions as an inducer of Cytochrome P450 (CYP) enzymes, primarily CYP2D6. This induction increases the cellular concentration of the enzyme in the liver, thereby accelerating the metabolic clearance rate of other compounds that serve as CYP2D6 substrates. This process influences the systemic concentration and subsequent physiological effects of co-administered drugs.

Dosage and Administration Information

The Regulatory Status of Glutethimide Administration

Glutethimide (formerly marketed as Doriden) is classified as a Schedule II controlled substance. This classification is reserved for drugs with a high potential for abuse, which may lead to severe psychological or physical dependence.

Glutethimide is officially listed as a discontinued human drug product. This means that the product's New Drug Application (NDA) has been withdrawn, and the drug is no longer actively marketed for use in patients, nor are current official prescribing information (like the package insert or SmPC) maintained in major regulatory databases.

Due to this discontinued status, current governmental regulatory documents do not provide active, explicit, or official instructions for use, which include:

  • Route of Administration: The drug was historically an oral tablet, but this is not a current official instruction.
  • Official Dosing Rules: Standard dose, frequency, and timing are not actively published by regulatory authorities.
  • Preparation or Special Conditions: Details regarding meal timing, preparation steps, or age-specific dosing are no longer officially documented for current patient use.

Any historical clinical administration information must be reviewed within the context of the drug's high abuse potential and the availability of newer, safer alternative therapies.

Recent Clinical Evidence

Glutethimide: Recent Clinical Evidence

Evidence for Use in Short-Term Insomnia Symptoms

Studies explored the compound’s application in the context of sleep initiation and maintenance difficulties. Controlled clinical trials were used in research exploring how symptoms change over time related to sleep onset and maintenance. These studies monitored outcomes related to systemic or functional imbalance, specifically by examining the time required to fall asleep (sleep latency) and the total duration of sleep. Researchers also used all-night EEG studies to examine patterns related to the compound and the different phases of the sleep cycle.

In these early trials, findings describe patterns observed in the studies related to sleep duration in the observed populations. The research describes patterns related to short-term sleep measures observed in the populations studied. These findings helped contextualize how patients reported their experience during periods of heightened symptom activity related to insomnia.

However, the certainty around these initial findings remains low to moderate. Most of the evidence is historical, and the follow-up durations were limited, typically spanning single-dose assessments or only a few weeks of use. This means there is limited information for long-term outcomes or the durability of the observed short-term changes. Comparative evidence is lacking with many of the therapies used today, and the evidence quality varies across studies due to the methodological standards of the era.

Evidence for Supportive Relief of Refractory Motor Symptoms

Research has also explored a more specialized application for the compound in patients experiencing certain conditions characterized by fluctuating or episodic manifestations, specifically action tremors. The study types available for this use differ significantly from the sleep trials, primarily consisting of open-label studies and small case series. These studies monitored outcomes reflecting daily functioning or activity level, focusing on measures of functional tremor severity.

The available evidence from these small case series data show patterns related to temporary changes in tremor severity measured in the observed populations. These studies often involved small, specialized cohorts of patients with conditions like Multiple Sclerosis or Traumatic Brain Injury. This research contributes to the broader evidence landscape by showing what has been observed so far in this specific context.

Long-Term Studies and Follow-Up Data

Research has examined the compound over defined time intervals, but the initial clinical trials were almost universally relevant in trials assessing short-term or episodic symptom patterns.

The research record contains limited information for long-term outcomes when the compound was observed in repeated use. Studies were not typically designed to assess the durability of any observed changes or the patterns of use over an extended period. Therefore, long-term effects are not fully established, and certainty remains low regarding continued use.

Evidence in Specialized Patient Groups

The majority of the available research was evaluated in adults. There is limited information that specifically details how the compound was studied for specific subgroups of adults with comorbidities or those at the extremes of age. Consequently, data for certain groups remain insufficient, and the results apply only to the populations studied in the original, often limited, trials.

Quality of Research and Remaining Uncertainties

The evidence base for Glutethimide is historical, and this contributes to the quality limitations. Evidence quality varies across studies, as the methodological standards, such as criteria for randomization and blinding in some older trials, may not align with current requirements for clinical research. The key uncertainties and limitations include the fact that follow-up durations were limited in almost all efficacy studies, and sample sizes were modest for many of the comparative trials. This research provides context but not individual predictions, as study results reflect the specific conditions under which they were conducted.

Frequently Asked Questions (FAQ)

Common questions about Glutethimide (FAQ)

Q: Does Glutethimide affect the function of other medicines when taken at the same time?

Yes, official product information indicates that Glutethimide is a potent inducer of liver microsomal enzymes. This process can increase the breakdown of certain co-administered medicines in the liver, potentially reducing their concentration in the bloodstream. This effect may alter how co-administered medications function.

Q: Can this drug be used in children or the elderly?

Regulatory documents state that this medicine is not recommended for use in the pediatric population (children). Official information also suggests that elderly patients may be especially sensitive to the effects of this type of medicine. Official guidance indicates that use in these specific populations requires explicit caution.

Q: What are the side effects related to the stomach or digestive system?

Documented effects on the gastrointestinal system from official sources include common reactions such as gastric irritation, nausea, diarrhea, and dry mouth.

Q: What is the exact chemical structure formula for Glutethimide?

The chemical nature of the compound is well-documented in regulatory and scientific summaries. Its exact chemical structure can be described by the IUPAC name 3-ethyl-3-phenylpiperidine-2,6-dione, and its molecular formula is C13H15NO2.

Q: Where does the drug name 'Glutethimide' come from?

The name of the drug, Glutethimide, is derived from specific chemical roots used in its nomenclature. These roots include "glut-" (related to its chemical class), "eth-" (referring to the ethyl group), and "-imide" (indicating the presence of an imide functional group).

Q: How long does the drug stay active in the body?

According to historical pharmacological data, this medicine is extensively metabolized, or broken down, by the liver. Its elimination half-life—the time it takes for half of the drug to be removed from the bloodstream—is estimated to be approximately 8 to 12 hours.

How should Glutethimide be stored and disposed of?

How to Store and Dispose of Glutethimide

Glutethimide must be stored at Controlled Room Temperature (CRT), defined as 20 C to 25 C (68 F to 77 F), with temporary excursions permitted up to 30 C.

Storage Requirements

Condition Requirement
Temperature Controlled Room Temperature
Container Tight container
Protection Protected from light
Safety Keep out of the reach of children

The official labeling mandates that the product be kept in a tight container and protected from light to maintain its stability. This medication must be stored safely, inaccessible to children.

Disposal

Unused or expired Glutethimide should be disposed of properly according to the guidance of a pharmacist or local waste disposal service. It should generally not be flushed down the toilet or poured into a drain, following standard medication disposal guidelines.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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