WARNINGOVERDOSE, COMBINATIONS, & WITHDRAWAL CAN BE FATAL
High doses alone or ordinary doses in combination with other depressants can fatally stop breathing. After prolonged dependency, stopping suddenly can cause seizures, delirium, or death.
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Hexobarbital
Hexobarbital is a barbiturate1 depressant with sedative and hypnotic effects1 and a short duration of action.2 It was used in the 1940s and 1950s to induce anesthesia for surgery3 and as a sleep-inducing drug.2 Other barbiturates have largely replaced it as an anesthetic because they offer better control over the depth of anesthesia.4 It may be habit-forming.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Dosage information for this substance remains poorly established and should be regarded as provisional.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Hexobarbital enhances GABA-A receptor activity through positive allosteric modulation at the barbiturate binding site, strengthening inhibitory signaling in the central nervous system. It increases GABA and benzodiazepine binding at their respective sites and prolongs chloride channel openings to the longest open state, reported as 9 milliseconds. The S-enantiomer of hexobarbital potentiates GABA-induced currents more potently than the R-enantiomer.5 Hexobarbital also blocks AMPA, kainate, and neuronal acetylcholine receptors, while open-channel blockade of P/Q-type voltage-gated calcium channels inhibits glutamate release and contributes to central nervous system depression.
Pharmacokinetics
Hexobarbital penetrates the central nervous system and undergoes hepatic metabolism through CYP2B1-catalyzed hydroxylation. This process is stereoselective: the S(+) enantiomer preferentially forms the β-hydroxylated product, while R(-) preferentially forms the α product, although both produce both forms. Hydroxylated metabolites undergo either glucuronidation by UDP-glucuronosyltransferases, facilitating excretion, or oxidation by a NAD(P)+-dependent dehydrogenase of the aldo-keto reductase family. In humans, this enzyme preferentially uses NAD+,6 and its activity is greatest toward the R(-) hydroxylated forms. Further metabolism proceeds through an epoxide-diol pathway, producing additional metabolites and a glutathione adduct. The estimated human plasma half-life is 222 ± 54 min;7 clearance of R(-) is almost ten times that of S(+), and average clearance is slower in older people than in younger people. The three major human metabolites are excreted mainly in urine, while the glutathione adduct is excreted in bile.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Addiction & Dependence
Psychological
HighClassified as habit-forming. Barbiturates as a class carry significant psychological addiction potential with regular use.
Physical
HighAs a barbiturate, hexobarbital is expected to produce physical dependence with chronic use. Barbiturate withdrawal can be severe and potentially life-threatening.
Toxicity
In severe overdose cases, coma and death can result. Specific lethal dose values are not documented in available sources.
Overdose produces progressive CNS depression including sluggishness, incoordination, difficulty thinking, slowed speech, impaired judgment, drowsiness progressing to coma, and shallow breathing.
May cause congenital abnormalities when used during pregnancy; classified as FDA Pregnancy Category D or C indicating potential teratogenic and fetotoxic effects.
History & Culture
Hexobarbital was sold under the names Citopan, Evipan, and Tobinal.8 In the 1940s and 1950s, it was used as an anesthetic for surgery3 and as a hypnotic in general medical practice. Hexobarbital was replaced by safer drugs, notably thiopental,…
Legality
References
Citations
Article Status
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