Flurothyl

From Wikipedia, the free encyclopedia

Template:Short description Template:Cs1 config Template:Short description Page Template:Infobox drug/styles.css has no content.

Page Module:Infobox/styles.css has no content.

Flurothyl
Lua error in package.lua at line 80: module 'Module:InfoboxImage/data' not found.
Clinical data
Trade namesIndoklon
Other namesHexafluorodiethyl ether
ATC codePage Template:Plainlist/styles.css has no content.
  • None
Identifiers
  • 2,2-Oxybis(1,1,1-trifluoroethane)
    or
    Bis(2,2,2-trifluoroethyl) ether
CAS NumberPage Template:Plainlist/styles.css has no content.
PubChem CIDPage Template:Plainlist/styles.css has no content.
PubChem SIDPage Template:Plainlist/styles.css has no content.
IUPHAR/BPSPage Template:Plainlist/styles.css has no content.
DrugBankPage Template:Plainlist/styles.css has no content.
ChemSpiderPage Template:Plainlist/styles.css has no content.
UNIIPage Template:Plainlist/styles.css has no content.
KEGGPage Template:Plainlist/styles.css has no content.
ChEBIPage Template:Plainlist/styles.css has no content.
ChEMBLPage Template:Plainlist/styles.css has no content.
NIAID ChemDBPage Template:Plainlist/styles.css has no content.
PDB ligandPage Template:Plainlist/styles.css has no content.
CompTox Dashboard (EPA)Page Template:Plainlist/styles.css has no content.
Chemical and physical data
FormulaC4H4F6O
Molar mass182.065 g·mol−1
3D model (JSmol)Page Template:Plainlist/styles.css has no content.
Density1.404 g/cm3
Boiling point62 to 63 °C (144 to 145 °F)
  • C(C(F)(F)F)OCC(F)(F)F
  • InChI=1S/C4H4F6O/c5-3(6,7)1-11-2-4(8,9)10/h1-2H2 ☒N
  • Key:KGPPDNUWZNWPSI-UHFFFAOYSA-N ☒N
Data page
Template:Infobox drug/data page link
Page Template:Nobold/styles.css has no content. ☒NcheckY (what is this?)Page Template:Nobold/styles.css has no content.  (verify)

Flurothyl (formerly under the trade name Indoklon) (IUPAC names: 1,1,1-trifluoro-2-(2,2,2-trifluoroethoxy)ethane or bis(2,2,2-trifluoroethyl) ether) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether and sevoflurane, but having the opposite effects, acting as a stimulant and convulsant.[1] A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.[2][3][4]

Several compounds related to the halogenated ether anesthetics have similar convulsant effects rather than producing sedation, and this has been helpful in studying the mechanism of action of these drugs.[5][6][7]

Currently, the main uses of flurothyl is in scientific research for inducing seizures in laboratory animals.[8] It is also sometimes used as an additive with the name of BTFE in lithium-ion batteries.[9][10]

Research into psychiatric treatment

Flurothyl was at one time used in psychiatric medicine for shock therapy, in a similar manner to other convulsant drugs such as pentetrazol, as an alternative to electroconvulsive therapy (ECT).[11][12] This use has now been discontinued.

In 1957, the Maryland pharmacologist J. C. Krantz experimented with flurothyl to induce seizures in psychiatric patients as an alternative to ECT. Flurothyl was injected into a plastic container in a tight fitting face mask. The patient inhaled a mixture of vapor and air, and expired air was forced into a charcoal adsorbent via a one-way valve. Oxygen was administered simultaneously. Flurothyl inhalations were first conducted without sedation or muscle paralysis.[13][14] Premedication with pentothal and succinylcholine chloride, as is customary in ECT, was tested and found safe.[15]

Four random assignment treatment studies found the clinical results for flurothyl to be as effective as those of ECT.[16][17][18][19] Flurothyl treatments were administered on the same schedules as ECT. In some patients who had not responded to ECT, flurothyl treatment produced improvement.[20]

The flurothyl treated patients showed less amnesia and confusion during the course of treatment with better patient acceptance. A detailed study comparing flurothyl and ECT in patients with severe endogenous depression, reported the degree of anterograde amnesia to be similar, but the degree of retrograde amnesia was much lower after flurothyl.[19] Psychological tests showed memory impairments at the fourth week of treatment, and memory improvement two weeks after the last treatment, with no measurable differences between the treatments.

Equal degrees of EEG slow wave increases were recorded in flurothyl and electrical induced seizures.[21] Oximetric and ECG studies showed comparable heart rate increases with occasional rhythmic irregularities.[17]

Flurothyl induced seizures were deemed clinically equal to electrical seizures with lesser effects on cognition and memory. An editorial in the Journal of the American Medical Association in 1966 encouraged its use.[22]

An injectable form of flurothyl was formulated.[23] The clinical results were the same as with inhaled flurothyl.[24]

Mechanism of action

The convulsant properties of flurothyl pose a challenge to unifying theories of general anesthetics such as the Meyer-Overton hypothesis (see Theories of general anaesthetic action).[25][26] A variety of halogenated ethers (e.g., isoflurane, sevoflurane) and diethyl ether itself are general anesthetics, and flurothyl is a substituted diethyl ether. Even more strikingly, a structural isomer of flurothyl known as isoflurothyl (1,1,1,3,3,3-hexafluoro-2-methoxypropane) induces general anesthesia and not convulsions in mice and dogs.[27] Isoflurothyl differs from the widely used inhalational anesthetic sevoflurane by only a single fluorine atom (sevoflurane has an additional fluorine on the methyl group).

A molecular explanation for the difference between flurothyl and isoflurothyl was provided by electrophysiology studies that showed flurothyl was an antagonist (blocker) of neuronal GABAA receptors and had no effect on neuronal glycine receptors.[28] This receptor selectivity resembles that of the well-characterized GABAA receptor antagonist picrotoxin. Studies using recombinant GABAA and glycine receptors confirmed this activity profile and further showed that isoflurothyl behaved similar to other ether anesthetics in acting as a positive allosteric modulator of GABAA and glycine receptors.[29] There is some evidence that flurothyl may actually possess general anesthetic properties at high concentrations that are masked by the more potent convulsant action.[27]

See also

References

Page Template:Reflist/styles.css has no content.

  1. ^ Page Module:Citation/CS1/styles.css has no content.Rose L, Watson A (July 1967). "Flurothyl (Indoklon). Experience with an inhalational convulsant agent". Anaesthesia. 22 (3): 425–34. doi:10.1111/j.1365-2044.1967.tb02765.x. PMID 4951597. S2CID 5714209.
  2. ^ Page Module:Citation/CS1/styles.css has no content.Karliner W, Padula LJ (1962). "Further clinical studies of hexafluorodiethyl ether convulsive treatments". Journal of Neuropsychiatry. 3: 159–62. PMID 14453985.
  3. ^ Page Module:Citation/CS1/styles.css has no content.Speers L, Neeley AH (February 1963). "The synthesis, chemical and physical properties of Indoklon". Journal of Neuropsychiatry. 4: 153–6. PMID 13989984.
  4. ^ Page Module:Citation/CS1/styles.css has no content.Krantz JC, Loecher CK (1967). "ANESTHESIA LXX: effect of inert fluorinated agents on fluroxene and flurothyl". Anesthesia & Analgesia. 46 (3): 271-274. doi:10.1213/00000539-196705000-00001. ISSN 0003-2999. Retrieved 2026-01-17.
  5. ^ Page Module:Citation/CS1/styles.css has no content.Koblin DD, Chortkoff BS, Laster MJ, Eger EI, Halsey MJ, Ionescu P (December 1994). "Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis". Anesthesia and Analgesia. 79 (6): 1043–8. doi:10.1213/00000539-199412000-00004. PMID 7978424.
  6. ^ Page Module:Citation/CS1/styles.css has no content.Koblin DD, Laster MJ, Ionescu P, Gong D, Eger EI, Halsey MJ, et al. (May 1999). "Polyhalogenated methyl ethyl ethers: solubilities and anesthetic properties". Anesthesia and Analgesia. 88 (5): 1161–7. doi:10.1213/00000539-199905000-00036. PMID 10320188.
  7. ^ Page Module:Citation/CS1/styles.css has no content.Eger EI, Halsey MJ, Harris RA, Koblin DD, Pohorille A, Sewell JC, et al. (June 1999). "Hypothesis: volatile anesthetics produce immobility by acting on two sites approximately five carbon atoms apart". Anesthesia and Analgesia. 88 (6): 1395–400. doi:10.1213/00000539-199906000-00036. PMID 10357351.
  8. ^ Page Module:Citation/CS1/styles.css has no content.Hashimoto Y, Araki H, Suemaru K, Gomita Y (May 2006). "Effects of drugs acting on the GABA-benzodiazepine receptor complex on flurothyl-induced seizures in Mongolian gerbils". European Journal of Pharmacology. 536 (3): 241–247. doi:10.1016/j.ejphar.2006.02.036. PMID 16581068.
  9. ^ Page Module:Citation/CS1/styles.css has no content.Gordin ML, Dai F, Chen S, Xu T, Song J, Tang D, et al. (June 2014). "Bis(2,2,2-trifluoroethyl) ether as an electrolyte co-solvent for mitigating self-discharge in lithium-sulfur batteries". ACS Applied Materials & Interfaces. 6 (11): 8006–8010. doi:10.1021/am501665s. PMID 24833106.
  10. ^ Page Module:Citation/CS1/styles.css has no content.Jiang LL, Yan C, Yao YX, Cai W, Huang JQ, Zhang Q (February 2021). "Inhibiting Solvent Co-Intercalation in a Graphite Anode by a Localized High-Concentration Electrolyte in Fast-Charging Batteries". Angewandte Chemie. 60 (7): 3402–3406. doi:10.1002/anie.202009738. PMID 33107707.
  11. ^ Page Module:Citation/CS1/styles.css has no content."A convulsant agent for psychiatric use. Flurothyl (Indoklon)". JAMA. 196 (1): 29–30. April 1966. doi:10.1001/jama.196.1.29. PMID 4379572.
  12. ^ Page Module:Citation/CS1/styles.css has no content.Small JG, Small IF, Sharpley P, Moore DF (July 1968). "A double-blind comparative evaluation of flurothyl and ECT". Archives of General Psychiatry. 19 (1): 79–86. doi:10.1001/archpsyc.1968.01740070081012. PMID 5658383.
  13. ^ Page Module:Citation/CS1/styles.css has no content.Esquibel AJ, Krantz JC, Truitt EB, Ling AS, Kurland AA (June 1958). "Hexafluorodiethyl ether (indoklon): its use as a convulsant in psychiatric treatment". The Journal of Nervous and Mental Disease. 126 (6): 530–4. doi:10.1097/00005053-195806000-00004. PMID 13564231. S2CID 2650010.
  14. ^ Page Module:Citation/CS1/styles.css has no content.Krantz JC, Esquibel A, Truitt EB, Ling AS, Kurland AA (March 1958). "Hexafluorodiethyl ether (indoklon); an inhalant convulsant; its use in psychiatric treatment". Journal of the American Medical Association. 166 (13): 1555–62. doi:10.1001/jama.1958.02990130015004. PMID 13513394.
  15. ^ Page Module:Citation/CS1/styles.css has no content.Karliner WJ, Padina LJ (1959). "Indoklon combined with Pentothal and Anectine". Am. J. Psychiatry. 115 (11): 1041–1042. doi:10.1176/ajp.115.11.1041.
  16. ^ Page Module:Citation/CS1/styles.css has no content.Fink M, Kahn RL, Karp E, Pollack M, Green MA, Alan B, et al. (March 1961). "Inhalant-induced convulsions. Significance for the theory of the convulsive therapy process". Archives of General Psychiatry. 4 (3): 259–66. doi:10.1001/archpsyc.1961.01710090045006. PMID 13699611.
  17. ^ a b Page Module:Citation/CS1/styles.css has no content.Kurland AA, Hanlon TE, Esquibel AJ, Krantz JC, Sheets CS (July 1959). "A comparative study of hexafluorodiethyl ether (indoklon) and electroconvulsive therapy". The Journal of Nervous and Mental Disease. 129: 95–98. doi:10.1097/00005053-195907000-00016. PMID 14412877.
  18. ^ Page Module:Citation/CS1/styles.css has no content.Small JG, Small IF, Sharpley P, Moore DF (July 1968). "A double-blind comparative evaluation of flurothyl and ECT". Archives of General Psychiatry. 19 (1): 79–86. doi:10.1001/archpsyc.1968.01740070081012. PMID 5658383.
  19. ^ a b Page Module:Citation/CS1/styles.css has no content.Laurell B (1970). "Flurothyl convulsive therapy". Acta Psychiatrica Scandinavica. Supplementum. 213: 1–79. PMID 4394881.
  20. ^ Page Module:Citation/CS1/styles.css has no content.Karliner W, Padula LJ (1960). "The use of hexafluorodiethyl ether in psychiatric treatment". Journal of Neuropsychiatry. 2: 67–70. PMID 13751512.
  21. ^ Page Module:Citation/CS1/styles.css has no content.Fink M (1979). Convulsive Therapy: Theory and Practice. New York: Raven Press.
  22. ^ Page Module:Citation/CS1/styles.css has no content."A convulsant agent for psychiatric use. Flurothyl (Indoklon)". JAMA. 196 (1): 29–30. April 1966. doi:10.1001/jama.196.1.29. PMID 4379572.
  23. ^ Page Module:Citation/CS1/styles.css has no content.Krantz JC, Manchey LL, Truitt EB, Ling AS, Kurland AA (July 1959). "The availability of hexafluorodiethyl ether by intravenous injection as a convulsant in psychiatric treatment". The Journal of Nervous and Mental Disease. 129: 92–4. doi:10.1097/00005053-195907000-00015. PMID 14411701.
  24. ^ Page Module:Citation/CS1/styles.css has no content.Karliner W (February 1963). "Clinical experiences with intravenous Indoklon: a new convulsant drug". Journal of Neuropsychiatry. 4: 184–9. PMID 13962526.
  25. ^ Page Module:Citation/CS1/styles.css has no content.Koblin DD, Chortkoff BS, Laster MJ, Eger EI, Halsey MJ, Ionescu P (December 1994). "Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis". Anesthesia and Analgesia. 79 (6): 1043–8. doi:10.1213/00000539-199412000-00004. PMID 7978424.
  26. ^ Page Module:Citation/CS1/styles.css has no content.Krasowski MD (July 2003). "Contradicting a unitary theory of general anesthetic action: a history of three compounds from 1901 to 2001". Bulletin of Anesthesia History. 21 (3): 1, 4–8, 21 passim. doi:10.1016/s1522-8649(03)50031-2. PMC 2701367. PMID 17494361.
  27. ^ a b Page Module:Citation/CS1/styles.css has no content.Koblin DD, Eger EI, Johnson BH, Collins P, Terrell RC, Speers L (July 1981). "Are convulsant gases also anesthetics?". Anesthesia and Analgesia. 60 (7): 464–70. doi:10.1213/00000539-198107000-00002. PMID 7195661.
  28. ^ Page Module:Citation/CS1/styles.css has no content.Wakamori M, Ikemoto Y, Akaike N (December 1991). "Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat". Journal of Neurophysiology. 66 (6): 2014–21. doi:10.1152/jn.1991.66.6.2014. PMID 1667416.
  29. ^ Page Module:Citation/CS1/styles.css has no content.Krasowski MD (April 2000). "Differential modulatory actions of the volatile convulsant flurothyl and its anesthetic isomer at inhibitory ligand-gated ion channels". Neuropharmacology. 39 (7): 1168–83. doi:10.1016/s0028-3908(99)00221-x. PMC 2846390. PMID 10760360.

Lua error in package.lua at line 80: module 'Module:Navbox/configuration' not found. Template:Convulsants

Retrieved from "https://cosmopedia.co/index.php?title=Flurothyl&oldid=6438442"