RESEARCH MONOGRAPH · KDC-MN-1305
Enflurane
Enflurane is the immediate predecessor to isoflurane in Ross Terrell's halogenated ether series, with both molecules emerging within two years of each other (1963 and 1965). It reached clinical use in 1972 as Ethrane and was widely used through the 1980s. The mechanism mirrors other volatiles, but enflurane has a peculiar quirk: at end-tidal concentrations above 2.5 percent and especially during low CO2 levels, it produces high-amplitude epileptiform activity on EEG and occasional clinical seizures during deep anesthesia. The mechanism appears to involve thalamocortical disinhibition. This contraindicates the agent in epilepsy patients and was the principal reason isoflurane (the structural isomer with similar profile but no seizure signal) displaced it. Clinical use has nearly disappeared in developed economies. 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 Kodiac editorial, not peer-reviewed.
Halogenated ether volatile general anesthetic
The immediate predecessor to isoflurane in the Terrell ether series, marketed as Ethrane, displaced by isoflurane owing to electroencephalographic seizure activity at high concentrations.
Abstract
Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether; CAS 13838-16-9; molecular formula C3H2ClF5O; molecular weight 184.49) is a halogenated methyl ethyl ether developed by Ross Terrell at Ohio Medical Products in the structure-activity series that produced both enflurane (1963) and its structural isomer isoflurane (1965). Enflurane reached clinical use in 1972 (Ethrane) and was widely used through the 1980s before isoflurane displaced it. The minimum alveolar concentration (MAC) at age 40 is 1.68 percent in oxygen; the blood-gas partition coefficient is 1.9, intermediate between halothane and isoflurane. Mechanism parallels other volatile anesthetics (GABA-A, K2P, glycine, NMDA modulation). The principal clinical limitation is dose-dependent generation of high-amplitude epileptiform activity on electroencephalography, particularly at end-tidal concentrations above 2.5 percent and during hypocapnia, with occasional clinical seizures during deep anesthesia. The mechanism of enflurane epileptogenesis is incompletely characterized but appears to involve thalamocortical disinhibition at concentrations where cortical inhibition exceeds cortical excitatory tone. This electrophysiological profile contraindicates enflurane in patients with seizure disorders and contributed substantially to its displacement by isoflurane, the structural isomer with similar clinical profile but absent the epileptiform signal. Hepatic metabolism is approximately 2 to 5 percent (intermediate between halothane and isoflurane); fluoride generation is sufficient to raise plasma concentrations into the historically nephrotoxic range during very prolonged exposures. Cardiovascular effects include modest myocardial depression and dose-dependent vasodilation. Clinical use of enflurane has nearly disappeared in developed economies; it remains available as a research tool for halogenated ether structure-activity studies.
Mechanism of action
Standard volatile profile (GABA-A, K2P, glycine, NMDA) with additional dose-dependent epileptiform EEG activity attributed to thalamocortical disinhibition at deep anesthetic concentrations.
Reported research dose ranges
Reported research dose ranges vary across the published literature.
References
- Virtue RW, Lund LO. A new ether-type general anesthetic agent: enflurane. Anesthesiology 1968.
- Neigh JL, et al. The electroencephalographic pattern during anesthesia with Ethrane. Anesthesiology 1971.
- Mazze RI, et al. Renal toxicity of enflurane. Anesthesiology 1977.
Read the full monograph
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.