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    Pentobarbital molecular structure

    Pentobarbital Stats & Data

    Nembutal Novopentobarb Pentobarbitone Yellow jackets
    Chemical Class medicine
    Psychoactive Class Depressant

    Pharmacology

    DrugBank
    Half-life 5 to 50 hours (dose dependent) State Solid

    Description

    A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)

    Mechanism of Action

    Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.

    Pharmacodynamics

    Pentobarbital, a barbiturate, is used for the treatment of short term insomnia. It belongs to a group of medicines called central nervous system (CNS) depressants that induce drowsiness and relieve tension or nervousness. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.

    Metabolism

    by hepatic microsomal enzyme system

    Absorption

    Barbiturates are absorbed in varying degrees following oral, rectal, or parenteral administration.

    Toxicity

    Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.

    Indication

    For the short-term treatment of insomnia.

    Elimination

    Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine, and less commonly, in the feces. Approximately 25 to 50 percent of a dose of aprobarbital or phenobarbital is eliminated unchanged in the urine, whereas the amount of other barbiturates excreted unchanged in the urine is negligible.

    Receptor Profile

    Receptor Actions

    Antagonists
    AMPA receptor antagonist
    Modulators
    GABA-A receptor positive allosteric modulator (barbiturate site)

    Receptor Binding

    Gamma-aminobutyric acid receptor subunit alpha-1 potentiator
    Gamma-aminobutyric acid receptor subunit alpha-2 potentiator
    Gamma-aminobutyric acid receptor subunit alpha-3 potentiator
    Gamma-aminobutyric acid receptor subunit alpha-4 potentiator
    Gamma-aminobutyric acid receptor subunit alpha-5 potentiator
    Gamma-aminobutyric acid receptor subunit alpha-6 potentiator
    Neuronal acetylcholine receptor subunit alpha-4 antagonist
    Neuronal acetylcholine receptor subunit alpha-7 antagonist
    Glutamate receptor 2 antagonist
    Glutamate receptor ionotropic, kainate 2 antagonist
    NMDA receptor antagonist

    History & Culture

    1930–present

    Pentobarbital was developed by chemists Ernest H. Volwiler and Donalee L. Tabern at Abbott Laboratories in 1930. That same year, physician John S. Lundy began clinical use of the compound and coined the brand name Nembutal, an amalgamation derived from the structural formula of its sodium salt—Na (sodium) combined with ethyl, methyl, butyl, and the common barbiturate suffix -al. The drug rapidly established itself in clinical practice as a sedative, short-term hypnotic, preanesthetic agent, and emergency anticonvulsant.

    1930s–present

    Pentobarbital became a widely abused pharmaceutical beginning in the late 1930s. Abbott's Nembutal capsules acquired the street name "yellow jackets" owing to the distinctive yellow color of the branded capsules. The formulation was available in 30, 50, and 100 mg capsules in yellow, white-orange, and yellow colors respectively, and the drug remained a commonly misused sedative throughout the mid-twentieth century.

    1999–present

    Abbott Pharmaceutical ceased production of their Nembutal-branded pentobarbital capsules in 1999, reflecting a broader transition in clinical practice as the benzodiazepine family of drugs supplanted barbiturates for most sedative and anxiolytic applications. Pentobarbital retained utility in veterinary medicine as an anesthetic and euthanasia agent. The injectable formulation continues to be manufactured, with Danish pharmaceutical company Lundbeck (now produced through Akorn Pharmaceuticals) remaining the sole supplier of injectable pentobarbital approved for sale in the United States.

    Pentobarbital has become a primary agent in physician-assisted death protocols across several jurisdictions. In the Netherlands, it constitutes part of the standard protocol for voluntary euthanasia, administered as a 9-gram oral solution in sugar syrup and alcohol following an antiemetic to prevent vomiting. Swiss protocols utilize intravenous sodium pentobarbital administration, which induces unconsciousness within approximately 30 seconds and cardiac arrest within 3 minutes. In the United States, oral pentobarbital is employed for physician-assisted death in states including Oregon, Washington, Vermont, and California.

    2010–present

    Pentobarbital entered use in capital punishment following the 2011 cessation of sodium thiopental production by its sole U.S. manufacturer, which rendered importation of that traditional execution drug impractical. Pentobarbital was first employed in a U.S. execution in December 2010 in Oklahoma as part of a three-drug protocol. In March 2011, Ohio became the first jurisdiction to utilize pentobarbital as the sole lethal injection agent. This application generated significant international controversy. When Lundbeck discovered its product was being used for executions—a practice illegal under Danish law—public outcry in Danish media prompted the company to cease sales to U.S. states practicing capital punishment and to prohibit distributors from supplying any entities participating in human executions. Despite these supply complications, multiple U.S. jurisdictions adopted pentobarbital protocols. Texas implemented a single-drug pentobarbital protocol in July 2012 following shortages of pancuronium bromide. Missouri modified its protocol in October 2013 to permit pentobarbital obtained from compounding pharmacies. In July 2019, U.S. Attorney General William Barr authorized the federal government to resume capital punishment after a 16-year suspension, with the federal protocol specifying intravenous administration of two syringes each containing 2.5 grams of pentobarbital sodium.

    Tolerance & Pharmacokinetics

    drugs.wiki

    Tolerance Decay

    Full tolerance 3d Half tolerance 37d Baseline ~60d

    Experience Report Analysis

    Erowid
    4 Reports
    2001–2011 Date Range
    3 With Age Data
    1 Effects Detected

    Demographics

    Gender Distribution

    Age Distribution

    Reports Over Time

    Effect Analysis

    Erowid

    Effects aggregated from 4 experience reports (4 Erowid)

    4 Reports
    1 Effects Detected
    1 Positive
    0 Adverse
    0 Neutral

    Effect Sentiment Distribution

    Confidence Distribution

    Positive Effects 1

    Stimulation 75.0% 70%

    Adverse Effects 0

    Real-World Dose Distribution

    62K Doses

    From 4 individual dose entries

    Legal Status

    UN Convention on Psychotropic Substances 1971 (Schedule III)
    Country Status Notes
    Australia Schedule 8 Controlled drug under Australian scheduling. Schedule 8 substances are available for therapeutic use but require strict prescribing and record-keeping requirements due to abuse potential.
    Canada Schedule IV CDSA Controlled under the Controlled Drugs and Substances Act. Available for legitimate medical use with appropriate authorization. Historically marketed in combination products.
    Germany Anlage III BtMG Listed in Anlage III of the Betäubungsmittelgesetz (Narcotics Act), indicating it is a marketable narcotic with recognized medical applications. Prescriptions require a special narcotic prescription form (Betäubungsmittelrezept).
    Russia Schedule II Controlled substance under federal narcotics legislation. Subject to strict regulation with limited availability for medical purposes.
    Switzerland Verzeichnis B Specifically named controlled substance under Verzeichnis B of Swiss narcotics legislation. Medicinal use is permitted with appropriate medical authorization.
    United Kingdom Class B Controlled under the Misuse of Drugs Act 1971. Unauthorized possession, supply, and production carry criminal penalties, though less severe than Class A substances.
    United States Schedule II Controlled under the Controlled Substances Act. Classified as having high potential for abuse but with currently accepted medical use. Approved for short-term treatment of insomnia and widely used in veterinary medicine. Available by prescription in injectable formulations.
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