Flurothyl

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Flurothyl
Flurothyl.png
Systematic (IUPAC) name
2,2-oxybis(1,1,1-trifluoroethane)
OR
bis(2,2,2-trifluoroethyl) ether
Clinical data
Legal status ?
Identifiers
CAS number 333-36-8 YesY
ATC code None
PubChem CID 9528
UNII 9Z467FG2YK YesY
Synonyms Hexafluorodiethyl ether
Chemical data
Formula C4H4F6O 
Mol. mass 182.064
Physical data
Density 1.404 g/cm3 g/cm³
 YesY (what is this?)  (verify)

Flurothyl (Indoklon) is a volatile liquid agent from the halogenated ether family, a congener of inhaled anaesthetic agents such as diethyl ether. At higher doses, after inducing loss of consciousness, these agents elicit a grand mal seizure, acting as both stimulant and convulsant.[1] Several compounds related to the halogenated ether anesthetics have similar convulsant effects. They have been helpful in studying the mechanism of action of these drugs.[2][3][4]

Flurothyl treatment in psychiatric patients In 1953 the Maryland pharmacologist J. C. Krantz experimented with flurothyl to induce seizures in psychiatric patients as an alternative treatment for electroconvulsive treatment (electroshock). Flurothyl was given the proprietary name “Indoklon.” 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. [6-8]

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.[9,10] Premedication with pentothal and succinylcholine chloride, as is customary in ECT, was tested and found safe. [11]

Four random assignment treatment studies found the clinical results for flurothyl to be as effective as those of ECT. [12-15] Flurothyl treatments were administered on the same schedules as ECT. In some patients who had not responded to ECT, flurothyl treatment produced improvement. [16]

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. [15] 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. [17] Oximetric and ECG studies showed comparable heart rate increases with occasional rhythmic irregularities. [13]

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. [18]

An injectable form of flurothyl was formulated. [19] The clinical results were the same as with inhaled flurothyl. [20]

The administration of flurothyl was more difficult than that of electrical inductions. The ethereal odors that quickly pervaded the treatment room frightened the treatment team members who saw how quickly, after a few breaths, the seizure was induced in patients. And the cost was greater. Flurothyl use was discarded in psychiatric patients for problems in administration, not inefficacy or risk.

Considering the persisting stigma and complaints of memory loss that continue to plague ECT, re-appraisal of flurothyl inhalation treatment in modern anesthesia suites has been encouraged. [21]

Its principal use in scientific studies is to induce seizures in animals.

See also: Theories of general anaesthetic action. Electroconvulsive therapy

See also: Theories of general anaesthetic action.

References[edit]

1. Rose, L, Watson, A (1967). "Flurothyl (Indoklon). Experience with an inhalational convulsant agent". Anaesthesia 22 (3): 425–34. PMID 4951597.

2. Koblin DD, Chortkoff BS, Laster MJ, et al. (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.

3. Koblin DD, Laster MJ, Ionescu P, 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.

4. Eger EI, Halsey MJ, Harris RA, 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.

5. Krantz, J. C. Jr., Carr, C. J., Lu, G., et al. . The anesthetic action of trifluoroethyl vinyl ether. J. Pharmacol. Exp. Ther. 1953; 108:488-495.

6. Karliner, W, Padula, L. Further clinical studies of hexafluorodiethyl ether convulsive treatments. J. Neuropsychiatry 1962; 3:159-162.

7. Speers, L, Neeley, A. H. The synthesis, chemical and physical properties of Indoklon. J. Neuropsychiatry 1963; 4:153-156.

8. Krantz, J. C. Jr., Loecher, C. K. Anesthesia LXX: effect of inert fluorinated agents on fluroxene and flurothyl. Anesthesia and Analgesia, 46(3):271-274, 1967.

9. Esquibel, A., Krantz, J. C. Jr., Truitt, et al. Hexafluorodiethyl ether (Indoklon) – Its use as a convulsant in psychiatric treatment. J. Nerv. Ment. Dis. 1958: 126:530-534.

10. Krantz, J. C. Jr., Esquibel, A., Truitt, A. et al. Hexafluorodiethyl ether (Indoklon) – an inhalant convulsant: Its use in psychiatric treatment. JAMA 1958: 166:1555-1556.

11. Karliner, W. Padula, L. Indoklon combined with Pentothal and Anectine. Am. J.Psychiatry, 1959; 115:1041-1042.

12. Fink, M., Kahn, R. L., Karp, E., et al. Inhalant-induced convulsions: Significance forthe theory of the convulsive therapy process. Arch. Gen. Psychiatry 1961; 4:259-266.

13. Kurland, A. A., Hanlon, T. E., Esquibel, A. J., et al. A comparative study of hexafluorodiethyl ether (Indoklon) and electroconvulsive therapy. J. Nerv. Ment. Dis. 1959; 129:95-98.

14. Small, J. G., Small, I. F., Sharply, P., and Moore, D. F. A double-blind comparative evaluation of flurothyl and ECT. Arch. Gen. Psychiatry, 1968; 19:79-86.

15. Laurell, B. (Ed.): Flurothyl convulsive therapy. Acta Psychiatr. Scand. [Suppl.], 213:1-79, 1970.

16. Karliner, W. and Padula, L. The use of hexaflourodiethyl ether in psychiatric treatment. J. Neuropsychiatry 1960; 2:67-70.

17. Fink M. Convulsive Therapy: Theory and Practice. New York: Raven Press, 1979.

18.A convulsant agent for psychiatric use. Flurothyl (Indoklon). JAMA: the Journal of the American Medical Association 196 (1): 29–30. 1966. doi:10.1001/jama.196.1.29. PMID 4379572.

19. Krantz, J. C. Jr., Manchey, L. L., Truitt, E. B., et al. The availability of hexafluorodiethyl ether by intravenous injection as a convulsant in psychiatric treatment. J. Nerv. Ment. Dis.1959; 128:92-94.

20. Karliner, W. Clinical experience with intravenous Indoklon: A new convulsant drug. J. Neuropsychiatry 1963; 4:184-189.

21. Cooper K, Fink M. The chemical induction of seizures in psychiatric therapy: Were flurothyl (Indoklon) and pentylenetetrazol (Metrazol) abandoned prematurely? J Clinical Psychopharmacology (in press 2014).