RESEARCH MONOGRAPH · KDC-MN-1321
Methohexital
Methohexital sodium (Brevital) is an ultrashort-acting methylated oxybarbiturate introduced by Eli Lilly in 1960. It differs from thiopental in retaining oxygen at the 2-position (oxybarbiturate, not thiobarbiturate) and adding a methyl group on the N-1 nitrogen. The 1-methyl substitution speeds hepatic metabolism roughly four-fold, shortening elimination half-life to about four hours and giving faster awakening with minimal residual sedation after a single induction dose. The dominant modern use is electroconvulsive therapy: methohexital is the preferred ECT induction agent in many practices because it has minimal anticonvulsant effect at induction doses, while propofol and thiopental both raise seizure threshold and shorten ECT seizures. Cardiovascular and respiratory effects mirror thiopental. Standard barbiturate cautions apply (porphyria, the 1-methyl group does not eliminate porphyrinogenicity). Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Methylated oxybarbiturate intravenous anesthetic
An ultrashort-acting methylated oxybarbiturate with faster recovery than thiopental, used principally for electroconvulsive therapy and brief procedural anesthesia.
Abstract
Methohexital sodium (alpha-DL-1-methyl-5-allyl-5-(1-methyl-2-pentynyl)barbituric acid sodium; CAS 22151-68-4; molecular formula C14H17N2NaO3; molecular weight 284.29 free acid) is a methylated oxybarbiturate intravenous anesthetic synthesized by Eli Lilly in 1956 and introduced clinically as Brevital in 1960. The compound differs from thiopental in retaining oxygen at the 2-position (oxybarbiturate rather than thiobarbiturate) and carrying a methyl group on the N-1 nitrogen. The 1-methyl substitution accelerates hepatic metabolism (clearance approximately 4-fold faster than thiopental on a milligram basis) and shortens elimination half-life to approximately 4 hours, enabling faster awakening with minimal residual sedation after a single induction dose. Mechanism is GABA-A positive allosteric modulation at the barbiturate site, identical to thiopental. The principal clinical niches in modern practice are electroconvulsive therapy (where the brief duration enables rapid recovery in serial-ECT outpatient settings) and brief procedural sedation in patients with contraindications to propofol. Methohexital is the dominant induction agent for ECT in many practices owing to its minimal anticonvulsant effect at induction doses (versus propofol and thiopental, which raise seizure threshold and shorten ECT seizure duration, requiring higher electrical stimulus). Cardiovascular and respiratory effects are similar to thiopental. The principal historical safety concerns are myoclonus on injection (a propofol-class adverse event also seen with methohexital) and the standard barbiturate contraindications (porphyria; the 1-methyl substitution does not eliminate the porphyrinogenic effect).
Mechanism of action
GABA-A positive allosteric modulation at the barbiturate site. Faster hepatic metabolism than thiopental drives the shorter clinical duration.
Reported research dose ranges
Reported research dose ranges vary across the published literature.
References
- Reves JG, et al. Pharmacology of intravenous anesthetic induction drugs. Anesthesiology 2007.
- Folk JW, et al. Anesthesia for electroconvulsive therapy. J Anesth 2000.
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Available as a research-use-only PDF download.
The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.