Thiopental

5-Ethyl-5-(1-methylbutyl)-2-thiobarbituric acid

Pentothal, Thiopentone, Sodium pentothal, Sodium thiopental, Penthiobarbital

Psychoactive Class

Chemical Class

Barbiturate Thiobarbituric acid derivative

Thiopental is an ultrashort-acting barbiturate of the thiobarbituric acid class,¹ primarily used in clinical settings for the induction of general anesthesia, management of convulsions, and reduction of intracranial pressure.¹ Administered intravenously, it produces rapid-onset hypnosis and anesthesia but notably lacks analgesic properties¹ — small doses may actually lower the pain threshold.² It is considered habit-forming¹ and is also employed in medically induced comas.³

Dosage & Duration

Dosage

Clinical anesthesia induction typically requires 3-6 mg/kg; coma induction 20 mg/kg. Doses reflect medical anesthetic use; recreational dosing data not available.

Duration

Onset30-45 seconds

Offset5-10 minutes

After Effects1-24 hours

Half-life

3-26 hours

Subjective Effects

The experience is defined by an extremely rapid loss of consciousness, with hypnosis setting in within roughly 30 to 40 seconds of intravenous injection and no excitation phase preceding it. The state produced is one of anesthesia and hypnosis rather than pain relief; small doses can actually lower the pain threshold rather than raise it. Recovery from a single small dose is quick but accompanied by lingering drowsiness and gaps in memory, while repeated doses lead to progressively prolonged unconsciousness as the drug accumulates in fatty tissue and is slowly re-released.

Physical

The body load is one of profound central nervous system depression and sleep, without meaningful muscle relaxation or analgesia. At excessive doses or with too-rapid injection, dangerous drops in blood pressure and respiratory difficulties including apnea can occur.

Cognitive

The dominant cognitive features are the abrupt extinguishing of awareness on administration and unreliable memory surrounding the event, with retrograde amnesia reported after recovery.

Suppressions

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Thiopental acts primarily as a positive allosteric modulator at GABA-A receptors via the barbiturate binding site, increasing the duration of chloride ion channel opening and prolonging GABAergic inhibitory neurotransmission.¹⁴ As a barbiturate, it binds relatively non-selectively across a superfamily of ligand-gated ion channels: while it potentiates inhibitory GABA-A receptor currents, it blocks cation-permeable channels including neuronal nicotinic acetylcholine receptors at clinically relevant concentrations.⁵ Additional targets include ionotropic glutamate receptors (AMPA and kainate subtypes), which it antagonizes,⁶ and fatty-acid amide hydrolase 1 (FAAH1), which it inhibits.

Pharmacokinetics

Thiopental is highly lipophilic, with a lipid-water partition coefficient of approximately 10, and rapidly crosses the blood-brain barrier.⁴ Its brief clinical effect after a single intravenous dose results primarily from redistribution out of the central nervous system into muscle and adipose tissue, where it accumulates at concentrations 6 to 12 times greater than plasma levels.¹ The free fraction in blood is then extensively metabolized in the liver, with only 0.3% of an administered dose excreted unchanged in urine.⁷ Ring desulfuration generates the active metabolite pentobarbital at approximately 3 to 10% of parent drug concentrations, while additional oxidation and hydroxylation pathways produce pharmacologically inert carboxylic acids and alcohols.⁸ Approximately 80% of circulating thiopental is bound to plasma protein.¹ Elimination half-life estimates range from 3 to 26 hours, and the drug displays zero-order elimination kinetics during continuous infusion.⁷⁴

Interactions

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

1,2-BenzodiazepineAbaloparatideAbataceptAbrocitinibAcebutolol

TripSit

Tolerance

Cross Tolerance

Barbiturates, Other GABA-A receptor positive allosteric modulators

Harm Potential

Addiction & Dependence

Psychological

Moderate

Classified as habit-forming with dependency risk, though recreational abuse is rare.¹

Physical

Moderate

Carries a dependency risk as a barbiturate; recreational use is uncommon despite the potential for dependence.¹

Toxicity

Cardiovascular

Rapid or repeated intravenous injection can cause severe hypotension progressing to shock; this risk is heightened in trauma patients or those with pre-existing cardiovascular compromise.¹

Respiratory

Respiratory depression including apnea, laryngospasm, and coughing may occur with excessive or overly rapid injection.¹

Peripheral Tissue

Vesicant properties can cause severe tissue necrosis and sloughing if extravasated during intravenous injection; proper intravenous technique is essential to avoid local damage.¹⁹

History & Culture

Discovery and Development

Sodium thiopental was discovered in the early 1930s by Ernest H. Volwiler and Donalee L. Tabern while working for Abbott Laboratories.¹⁰ The compound was first administered to human beings on March 8, 1934, by Dr. Ralph M. Waters, who investigated its properties and…

Legality

By Country

United StatesPrescription medication (Withdrawn from market)

Previously FDA-approved as a prescription injectable anesthetic for intravenous administration.¹ As a barbiturate, it is subject to controlled substance regulations.¹⁹¹ The injectable formulation was withdrawn from the US pharmaceutical market in January 2011.¹²⁰

References

Source Pages

Citations

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