Methoxyflurane - wikipedia Methoxyflurane Methoxyflurane Clinical data Synonyms 2, 2 - dichloro - 1, 1 - difluoroethyl methyl ether Pregnancy category AU : C US : C ( Risk not ruled out ) Routes of administration Inhalation ATC code N02BG09 ( WHO ) Legal status Legal status AU : S4 ( Prescription only ) Pharmacokinetic data Metabolism 70 % Identifiers IUPAC name 2, 2 - dichloro - 1, 1 - difluoro - 1 - methoxyethane CAS Number 76 - 38 - 0 PubChem CID 4116 DrugBank DB01028 ChemSpider 3973 UNII 30905R8O7B KEGG D00544 ChEBI CHEBI : 6843 ChEMBL CHEMBL1341 ECHA InfoCard 100.000. 870 Chemical and physical data Formula C H Cl F O Molar mass 164.966 g / mol 3D model ( JSmol ) Interactive image SMILES ClC ( Cl ) C ( F ) ( F ) OC InChI InChI = 1S / C3H4Cl2F2O / c1 - 8 - 3 ( 6, 7 ) 2 ( 4 ) 5 / h2H, 1H3 Key : RFKMCNOHBTXSMU - UHFFFAOYSA - N ( what is this ? ) ( verify ) Methoxyflurane ( INN ), formerly marketed as Penthrane by Abbott Laboratories, is a halogenated ether that was in clinical use as a volatile inhalational anesthetic from its introduction by Joseph F. Artusio et al in 1960 until the late 1970s. It was first synthesized in the late 1940s by William T. Miller and his team of chemists following their involvement in the Manhattan Project. Methoxyflurane is an extremely potent and highly lipid - soluble anesthetic agent, characterized by very slow induction ( onset of action ) and emergence ( offset or dissipation ) times. It is non-flammable, has relatively mild hemodynamic effects, and it does not predispose the heart to rhythm disturbances. It is, however, a significant respiratory depressant. Methoxyflurane has powerful analgesic ( pain - relieving ) properties at well below full anesthetic doses. It was utilized in self - administration devices for obstetric analgesia, in a manner that foreshadowed the patient - controlled analgesia infusion pumps of today. The biodegradation of methoxyflurane produces inorganic fluoride and dichloroacetic acid ( DCAA ). The combined effects of these two compounds may be responsible for the toxicity of methoxyflurane to some of the major organs of the human body. Methoxyflurane was determined to be nephrotoxic ( damaging to the kidneys ) in a dose - dependent response and hepatotoxic ( damaging to the liver ) at anesthetic doses in 1973, and the drug was abandoned as a general anesthetic in the late 1970s. In 1999, the manufacturer discontinued distribution of methoxyflurane in the United States and Canada, and on September 6, 2005, the Food and Drug Administration determined that it should be withdrawn from the market for safety concerns. It is however still used in Australia as an emergency analgesic for the initial management of pain due to acute trauma, as well as for brief painful procedures such as changing of wound dressings or for transport of injured people. Contents 1 Medical use 2 Chemical and physical properties 3 Pharmacokinetics 4 Pharmacodynamics 5 Biodegradation and toxicity 6 History 7 Notes 8 References 9 Further reading 10 External links Medical use Methoxyflurane has been extensively used since the 1970s in Australia as an emergency analgesic for short - term use, mostly by the Australian and New Zealand Defence Forces, and the Australian ambulance services. The drug is currently only available from one manufacturer ( Medical Developments International, Melbourne, Victoria, Australia ). It is self - administered to children and adults using the Penthrox inhaler, a hand - held inhaler device, known as `` the green whistle ''. A non-opioid alternative to morphine, it is also easier to use than nitrous oxide. As of 2010, methoxyflurane was listed under the Pharmaceutical Benefits Scheme for the initial management of pain due to acute trauma, as well as for brief painful procedures such as changing of wound dressings or for patient transport. A portable, disposable, single - use inhaler device ( the Penthrox inhaler ), along with a single 3 milliliter brown glass vial of methoxyflurane is provided in doctor 's kits that allows conscious hemodynamically stable patients ( including children over the age of 5 years ) to self - administer the drug, under supervision. Each 3 milliliter dose lasts approximately 30 minutes. Pain relief begins after 6 -- 8 breaths and continues for several minutes after stopping inhalation. The maximum recommended dose is 6 milliliters per day or 15 milliliters per week because of the risk of cumulative dose - related nephrotoxicity, and it should not be used on consecutive days. Despite the potential for renal impairment when used at anesthetic doses, no significant adverse effects have been reported in the literature when it is used at the lower doses ( up to 6 milliliters ) used for producing analgesia and sedation. Due to the risk of organ ( especially renal ) toxicity, methoxyflurane is contraindicated in patients with pre-existing kidney disease or diabetes mellitus, and is not recommended to be administered in conjunction with tetracyclines or other potentially nephrotoxic or enzyme - inducing drugs. Chemical and physical properties Further information : Organofluorine Space - filling model ( three - dimensional molecular structure ) of methoxyflurane With a molecular formula of C H Cl F O and a condensed structural formula of CHCl CF OCH, the International Union of Pure and Applied Chemistry ( IUPAC ) name for methoxyflurane is 2, 2 - dichloro - 1, 1 - difluoro - 1 - methoxyethane. It is a halogenated ether in form of a clear, colorless liquid, and its vapor has a strong fruity aroma. It is miscible with ethanol, acetone, chloroform, diethyl ether, and fixed oils. It is soluble in rubber. With a minimum alveolar concentration ( MAC ) of 0.16 %, methoxyflurane is an extremely potent anesthetic agent. It is a powerful analgesic agent at well below full anesthetic concentrations. Because of its low volatility and very high boiling point ( 104.8 ° C at 1 atmosphere ), methoxyflurane has a low vapor pressure at ambient temperature and atmospheric pressure. It is therefore quite difficult to vaporize methoxyflurane using conventional anesthetic vaporizers. Property Value Boiling point ( at 1 atmosphere ) 104.8 ° C Minimum alveolar concentration ( MAC ) 0.16 % Vapor pressure ( mmHg at 20 ° C ) 22.5 Partition coefficient ( Blood : Gas ) 12 Partition coefficient ( Oil : Gas ) 950 Partition coefficient ( Oil : Water ) 400 Specific gravity at 25 ° C 1.42 Flash point 63 ° C Molecular weight ( g mol ) 164.97 Vapor - liquid equilibrium ( mL ) 208 Flammability limits 7 % in air Chemical stabilizer necessary Yes The carbon -- fluorine bond, a component of all organofluorine compounds, is the strongest chemical bond in organic chemistry. Furthermore, this bond becomes shorter and stronger as more fluorine atoms are added to the same carbon on a given molecule. Because of this, fluoroalkanes are some of the most chemically stable organic compounds. Pharmacokinetics Methoxyflurane has a very high lipid solubility ( oil : gas partition coefficient of around 950 ), which gives it very slow pharmacokinetics ( induction and emergence characteristics ) ; this being undesirable for routine application in the clinical setting. Initial studies performed in 1961 revealed that in unpremedicated healthy individuals, induction of general anesthesia with methoxyflurane - oxygen alone or with nitrous oxide was difficult or even impossible using the vaporizers available at that time. It was found to be necessary to administer an intravenous anesthetic agent such as sodium thiopental to ensure a smooth and rapid induction. It was further found that after thiopental induction, it was necessary to administer nitrous oxide for at least ten minutes before a sufficient amount of methoxyflurane could accumulate in the bloodstream to ensure an adequate level of anesthesia. This was despite using high flow ( liters / minute ) of nitrous oxide and oxygen, and with the vaporizers delivering the maximum possible concentration of methoxyflurane. Similar to its induction pharmacokinetics, methoxyflurane has very slow and somewhat unpredictable emergence characteristics. During initial clinical studies in 1961, the average time to emergence after discontinuation of methoxyflurane was 59 minutes after administration of methoxyflurane for an average duration of 87 minutes. The longest time to emergence was 285 minutes, after 165 minutes of methoxyflurane administration. Pharmacodynamics Cardiovascular effects The effects of methoxyflurane on the circulatory system resemble those of diethyl ether. In dogs, methoxyflurane anesthesia causes a moderate decrease in blood pressure with minimal changes in heart rate, and no significant effect on blood sugar, epinephrine, or norepinephrine. Bleeding and increased arterial partial pressure of carbon dioxide ( PaCO ) both induce further decreases in blood pressure, as well as increases in blood glucose, epinephrine and norepinephrine. In humans, methoxyflurane produces some decrease in blood pressure, but cardiac output, stroke volume, and total peripheral resistance are only minimally depressed. Its effect on the pulmonary circulation is negligible, and it does not predispose the heart to cardiac dysrhythmias. Respiratory effects Unlike diethyl ether, methoxyflurane is a significant respiratory depressant. In dogs, methoxyflurane causes a dose - dependent decrease in respiratory rate and a marked decrease in respiratory minute volume, with a relatively mild decrease in tidal volume. In humans, methoxyflurane causes a dose - dependent decrease in tidal volume and minute volume, with respiratory rate relatively constant. The net effect of these changes is profound respiratory depression, as evidenced by CO retention with a concomitant decrease in arterial pH ( this is referred to as a respiratory acidosis ) when anesthetized subjects are allowed to breathe spontaneously for any length of time. Gastrointestinal effects In a series of 500 consecutive obstetric patients, Boisvert and Hudon observed vomiting in 12 ( 4.8 % ) patients during or after administration of methoxyflurane anesthesia. These findings compared favorably with those reported for cyclopropane ( 42 % ), trichloroethylene ( 28 % ) and halothane ( 4.6 % ). In another study of 645 obstetric patients, Romagnoli and Korman observed 8 cases ( 1.2 % ) of postoperative vomiting, one of whom was retching before the administration of the anesthetic. Analgesic effects Although the high blood solubility of methoxyflurane is often undesirable, this property makes it useful in certain situations -- it persists in the lipid compartment of the body for a long time, providing sedation and analgesia well into the postoperative period. There is substantial data to indicate that methoxyflurane is an effective analgesic and sedative agent at subanesthetic doses. Supervised self - administration of methoxyflurane in children and adults can briefly lead to deep sedation, and it has been used as a patient controlled analgesic for painful procedures in children in hospital emergency departments. During childbirth, administration of methoxyflurane produces significantly better analgesia, less psychomotor agitation, and only slightly more somnolence than trichloroethylene. In 1968, Robert Wexler of Abbott Laboratories developed the Analgizer, a disposable inhaler that allowed the self - administration of methoxyflurane vapor in air for analgesia. The Analgizer consisted of a polyethylene cylinder 5 inches long and 1 inch in diameter with a 1 inch long mouthpiece. The device contained a rolled wick of polypropylene felt which held 15 milliliters of methoxyflurane. Because of the simplicity of the Analgizer and the pharmacological characteristics of methoxyflurane, it was easy for patients to self - administer the drug and rapidly achieve a level of conscious analgesia which could be maintained and adjusted as necessary over a period of time lasting from a few minutes to several hours. The 15 milliliter supply of methoxyflurane would typically last for two to three hours, during which time the user would often be partly amnesic to the sense of pain ; the device could be refilled if necessary. The Analgizer was found to be safe, effective, and simple to administer in obstetric patients during childbirth, as well as for patients with bone fractures and joint dislocations, and for dressing changes on burn patients. When used for labor analgesia, the Analgizer allows labor to progress normally and with no apparent adverse effect on Apgar scores. All vital signs remain normal in obstetric patients, newborns, and injured patients. The Analgizer was widely utilized for analgesia and sedation until the early 1970s, in a manner that foreshadowed the patient - controlled analgesia infusion pumps of today. The Analgizer inhaler was withdrawn in 1974, but use of methoxyflurane as a sedative and analgesic continues in Australia and New Zealand in the form of the Penthrox inhaler. Trials of methoxyflurane as an analgesic in emergency medicine are going on in the UK. Biodegradation and toxicity Further information : Drug metabolism and Fluoride poisoning The first report of nephrotoxicity appeared in 1964, when Paddock and colleagues reported three cases of acute renal insufficiency, two of whom were found to have calcium oxalate crystals in the renal tubules at autopsy. In 1966, Crandell and colleagues reported a series in which 17 / 95 ( 18 % ) of patients developed an unusual type of nephropathy after operations in which methoxyflurane was used as a general anesthetic. This particular type of renal insufficiency was characterized by vasopressin - resistant high - output renal failure ( production of large volumes of poorly concentrated urine ) with a negative fluid balance, pronounced weight loss, elevation of serum sodium, chloride, osmolality and blood urea nitrogen. The urine of these patients was of a relatively fixed specific gravity and an osmolality very similar to that of the serum. Furthermore, the high urine output persisted a challenge test of fluid deprivation. Most cases resolved within 2 -- 3 weeks, but evidence of renal dysfunction persisted for more than one year in 3 of these 17 cases ( 18 % ), and more than two years in one case ( 6 % ). Reports of severe and even fatal hepatotoxicity related to the use of methoxyflurane began to appear in 1966. These reports prompted anesthesiologists to subject this agent to intense and systematic scrutiny. A study published in 1973 by Cousins and Mazze demonstrated that compared with halothane, methoxyflurane produces dose - dependent and deleterious abnormalities in renal function. The authors showed that subclinical nephrotoxicity occurred following methoxyflurane at minimum alveolar concentration ( MAC ) for 2.5 to 3 hours ( 2.5 to 3 MAC hours ), while overt toxicity was present in all patients at dosages greater than five MAC hours. This landmark study provided a model that would be used for the assessment of the nephrotoxicity of volatile anesthetics for the next two decades. The biodegradation of methoxyflurane begins immediately after the onset of exposure. The kidney and liver toxicity observed after anesthetic doses is attributable to one or more metabolites produced by O - demethylation of methoxyflurane. Significant products of this catabolic process include methoxyfluoroacetic acid ( MFAA ), dichloroacetic acid ( DCAA ), and inorganic fluoride. Methoxyflurane nephrotoxicity is dose dependent and irreversible, resulting from O - demethylation of methoxyflurane to fluoride and DCAA. This effect is so predictable and reproducible that methoxyflurane now serves as a pharmacologic model of fluoride - related nephrotoxicity, one with which newer drugs are compared. It is not entirely clear whether the fluoride itself is toxic -- it may simply be a surrogate measure for some other toxic metabolite. The concurrent formation of inorganic fluoride and DCAA is unique to methoxyflurane biotransformation compared with other volatile anesthetics, and this combination is more toxic than fluoride alone. This may explain why fluoride formation from methoxyflurane is associated with nephrotoxicity, while fluoride formation from other volatile anesthetics ( such as enflurane and sevoflurane ) is not. Furthermore, the concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity. Based on the findings of these and other studies in the early 1970s, the current consensus is that the use of methoxyflurane should be restricted only to healthy individuals, in situations where it offers specific advantages and even then, only at dosages less than 2.5 MAC hours. Partly because of these warnings, but also because of the development of newer volatile anesthetics such as enflurane, isoflurane, desflurane and sevoflurane, the clinical use of methoxyflurane as a general anesthetic in humans was largely abandoned in the mid-1970s. The National Institute for Occupational Safety and Health maintains a recommended exposure limit for methoxyflurane as waste anesthetic gas of 2 ppm ( 13.5 mg / m ) over 60 minutes. History All of the currently used volatile anesthetic agents are organofluorine compounds. Aside from the synthesis of Freon ( Thomas Midgley, Jr. and Charles F. Kettering, 1928 ) and the discovery of Teflon ( Roy J. Plunkett, 1938 ), the field of organofluorine chemistry had not attracted a great deal of attention up to 1940 because of the extreme reactivity of elemental fluorine, which had to be produced in situ for use in chemical reactions. The development of organofluorine chemistry was a spin - off from the Manhattan Project, during which elemental fluorine was produced on an industrial scale for the first time. The need for fluorine arose from the need to separate the isotope U from U because the former, present in natural uranium at a concentration of less than 1 % is fissile ( capable of sustaining a nuclear chain reaction of nuclear fission with thermal neutrons ), whereas the latter is not. Members of the MAUD Committee ( especially Francis Simon and Nicholas Kurti ) proposed the use of gaseous diffusion for isotope separation, since, according to Graham 's law the rate of diffusion is inversely proportional to molecular mass. After an extensive search, uranium hexafluoride, UF, was determined to be the most suitable compound of uranium to be used for the gaseous diffusion process. Elemental fluorine is needed in the production of UF. Significant obstacles had to be overcome in the handling of both fluorine and UF. Before the K - 25 gaseous diffusion plant could be built, it was first necessary to develop non-reactive chemical compounds that could be used as coatings, lubricants and gaskets for the surfaces which would come into contact with the UF gas ( a highly reactive and corrosive substance ). William T. Miller, professor of organic chemistry at Cornell University, was co-opted to develop such materials, because of his expertise in organofluorine chemistry. Miller and his team developed several novel non-reactive chlorofluorocarbon polymers that were used in this application. Charles Suckling synthesized halothane in 1951. Halothane was the first organofluorine anesthetic agent to be introduced into clinical practice in 1956. Miller and his team continued to develop organofluorine chemistry after the end of World War II and methoxyflurane was synthesized in 1948. Notes ^ Jump up to : Miller Jr, WT ; Fager, EW ; Griswold, PH ( 1948 ). `` The Addition of Methyl Alcohol to Fluoroethylenes ''. 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PMID 3971205. ^ Jump up to : Cousins MJ, Mazze RI ( 1973 ). `` Methoxyflurane nephrotoxicity : a study of dose response in man ( abstract ) ''. Journal of the American Medical Association. 225 ( 13 ) : 1611 -- 6. doi : 10.1001 / jama. 1973.03220410023005. PMID 4740737. ^ Jump up to : Barash, Cullen and Stoelting ( 2009 ), Ebert and Schmid, Chapter 17 : Inhaled Anesthetics, pp. 413 -- 43 ^ Jump up to : Gottlieb LS, Trey C ( 1974 ). `` The effects of fluorinated anesthetics on the liver and kidneys ''. Annual Review of Medicine. 25 : 411 -- 29. doi : 10.1146 / annurev. me. 25.020174. 002211. PMID 4596236. Jump up ^ Jones NO ( 1972 ). `` Methoxyflurane nephrotoxicity -- a review and a case report '' ( PDF ). Canadian Anaesthetists ' Society Journal. 19 ( 2 ) : 152 -- 9. doi : 10.1007 / BF03005045. PMID 5029469. Jump up ^ Mazze RI ( 1976 ). `` Methoxyflurane nephropathy ''. Environmental Health Perspectives. 15 : 111 -- 9. doi : 10.2307 / 3428393. JSTOR 3428393. PMC 1475154. PMID 1001288. Jump up ^ Kharasch ED, Schroeder JL, Liggitt HD, Park SB, Whittington D, Sheffels P ( 2006 ). `` New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development ( part 1 ) : Identification of the nephrotoxic metabolic pathway ''. Anesthesiology. 105 ( 4 ) : 726 -- 36. doi : 10.1097 / 00000542 - 200610000 - 00019. PMID 17006072. Jump up ^ Kharasch ED, Schroeder JL, Liggitt HD, Ensign D, Whittington D ( 2006 ). `` New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development ( part 2 ) : Identification of nephrotoxic metabolites ''. Anesthesiology. 105 ( 4 ) : 737 -- 45. doi : 10.1097 / 00000542 - 200610000 - 00020. PMID 17006073. Jump up ^ Helsinn Birex Therapeutics Ltd ( 2009 ). `` By - Mycin 50mg capsules ''. medicines.ie : Medicines information online. Dublin, Ireland : Irish Pharmaceutical Healthcare Association Ltd. Retrieved 2011 - 06 - 12. Jump up ^ `` CDC - NIOSH Pocket Guide to Chemical Hazards - Methoxyflurane ''. www.cdc.gov. Retrieved 2015 - 11 - 19. Jump up ^ Sneader ( 2005 ), Sneader W, Chapter 8 : Systematic medicine, pp. 74 -- 87 Jump up ^ DuPont ( 2010 ). `` Roy Plunkett : 1938 ''. DuPont Heritage. Wilmington, Delaware : E.I. du Pont de Nemours and Company. Retrieved 2011 - 06 - 12. Jump up ^ Cotton ( 2006 ), Cotton S, Chapter 10 : Binary compounds of the actinides, pp. 155 -- 72 Jump up ^ Rhodes ( 1986 ), Rhodes R, Chapter 11 : Cross sections, pp. 318 -- 56 Jump up ^ Beaton L ( 1962 ). `` The slow - down in nuclear explosive production ''. New Scientist. 16 ( 309 ) : 141 -- 3. Jump up ^ Friedlander Jr., BP ( 3 December 1998 ). `` William T. Miller, Manhattan Project scientist and Cornell professor of chemistry, dies at 87 ''. Cornell News. Ithaca, New York : Cornell University. Archived from the original on 7 June 2011. Retrieved 2011 - 06 - 12. Jump up ^ Raventós, J ( 1956 ). `` The action of fluothane -- a new volatile anaesthetic ''. British Journal of Pharmacology and Chemotherapy. 11 ( 4 ) : 394 -- 410. doi : 10.1111 / j. 1476 - 5381.1956. tb00007. x. PMC 1510559. PMID 13383118. References Barash, PG ; Cullen, BF ; Stoelting, RK ; Cahalan, MK ; Stock, MC, eds. ( 2009 ). Clinical anesthesia ( 6th ed. ). Philadelphia : Lippincott Williams & Wilkins. ISBN 978 - 0 - 7817 - 8763 - 5. Cotton S ( 2006 ). Lanthanide and actinide chemistry ( 1st ed. ). Chichester, England : John Wiley and Sons, Ltd. ISBN 978 - 0 - 470 - 01006 - 8. Rhodes, R ( 1986 ). The making of the atomic bomb. New York : Simon & Schuster. ISBN 978 - 0 - 684 - 81378 - 3. Sneader W ( 2005 ). Drug discovery : a history. Chichester, England : John Wiley and Sons, Ltd. ISBN 978 - 0 - 471 - 89980 - 8. Further reading Brennan, R. ; Pearlstein, A. ; Miller, S. ( 1988 ). `` Computed tomography of the kidneys in a patient with methoxyflurane abuse ''. Journal of computer assisted tomography. 12 ( 1 ) : 155 -- 156. doi : 10.1097 / 00004728 - 198801000 - 00033. PMID 3335658. Clark, R. ; Beard, A. ; Thompson, D. ( 1979 ). `` Renal function in newborns and mothers exposed to methoxyflurane analgesia for labor and delivery ''. Anesthesiology. 51 ( 5 ) : 464 -- 466. doi : 10.1097 / 00000542 - 197911000 - 00020. PMID 496064. Corbett, T. ; Ball, G. ( 1971 ). `` Chronic exposure to methoxyflurane : A possible occupational hazard to anesthesiologists ''. Anesthesiology. 34 ( 6 ) : 532 -- 537. doi : 10.1097 / 00000542 - 197106000 - 00012. PMID 5556243. Crankshaw DP, Eagle A, Komesaroff D ( 2004 ). `` Methoxyflurane dosage with the Penthrox inhaler for analgesia during short painful procedures ( abstract ) ''. Anaesth. Intensive Care. 32 ( 3 ) : 428. Dahlgren, B. ( 1979 ). `` Fluoride concentrations in urine of delivery ward personnel following exposure to low concentrations of methoxyflurane ''. Journal of Occupational Medicine. 21 ( 9 ) : 624 -- 626. PMID 490224. Dahlgren, B. ( 1980 ). `` Hepatic and renal effects of low concentrations of methoxyflurane in exposed delivery ward personnel ''. Journal of Occupational Medicine. 22 ( 12 ) : 817 -- 819. doi : 10.1097 / 00043764 - 198012000 - 00017. PMID 7218059. Dahlgren, B. ; Olander, L. ; Ovrum, P. ( 1979 ). `` Pollution of delivery ward air by nitrous oxide -- methoxyflurane ''. American Industrial Hygiene Association journal. 40 ( 8 ) : 666 -- 672. doi : 10.1080 / 15298667991430136. PMID 495468. De Francisco, C. ( 1971 ). `` Pentrane dependence : A case report ''. The British Journal of Psychiatry. 119 ( 553 ) : 609 -- 610. doi : 10.1192 / bjp. 119.553. 609. PMID 5143658. Edmunds, D. ; Rosen, M. ( 1975 ). `` Inhalation sedation for conservative dentistry. A comparison between nitrous oxide and methoxyflurane ''. British dental journal. 139 ( 10 ) : 398 -- 402. doi : 10.1038 / sj. bdj. 4803643. PMID 1059442. Elder, B. ; Beal, H. ; Dewald, W. ; Cobb, S. ( 1971 ). `` Exacerbation of subclinical myasthenia by occupational exposure to an anesthetic ''. Anesthesia and Analgesia. 50 ( 3 ) : 383 -- 387. doi : 10.1213 / 00000539 - 197105000 - 00023. PMID 5103772. Kharasch, E. ; Hankins, D. ; Thummel, K. ( 1995 ). `` Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity ''. Anesthesiology. 82 ( 3 ) : 689 -- 699. doi : 10.1097 / 00000542 - 199503000 - 00011. PMID 7879937. Klemmer, P. ; Hadler, N. ( 1978 ). `` Subacute fluorosis : A consequence of abuse of an organofluoride anesthetic ''. Annals of Internal Medicine. 89 ( 5 Pt 1 ) : 607 -- 611. doi : 10.7326 / 0003 - 4819 - 89 - 5 - 607. PMID 717928. Komesaroff D ; Crankshaw DP ( 2004 ). Methoxyflurane analgesia with the Penthrox Inhaler : Emergency Department and Hospital Ward Applications. Teaching and Research Conference. Victoria University of Technology, Melbourne, Australia. Laird SM, Gray BM. Intermittent inhalation of methoxyflurane and trichloroethylene as an analgesic in burns dressings procedures. Br. J. Anaesth. 1971 ; 43 : 149 -- 59. Lindblad P, Zack M, Adami HO, Ericson A ( 1992 ). `` Maternal and perinatal risk factors for Wilms ' tumor : a nationwide nested case control study in Sweden ''. International Journal of Cancer. 51 ( 1 ) : 38 -- 41. doi : 10.1002 / ijc. 2910510108. PMID 1314230. Major, V. ; Rosen, M. ; Mushin, W. ( 1967 ). `` Concentration of methoxyflurane for obstetric analgesia by self - administered intermittent inhalation ''. British Medical Journal. 4 ( 5582 ) : 767 -- 770. doi : 10.1136 / bmj. 4.5582. 767. PMC 1749043. PMID 6081001. Metropolitan Ambulance Service / Rural Ambulance Service. Clinical practice guideline D020. Version 4, 2005. Methoxyflurane ( Penthrane ). Miller WT ( 1981 ). `` My early days in fluorine chemistry '' ( PDF ). Journal of Fluorine Chemistry. 18 ( 4 ) : 305 -- 21. doi : 10.1016 / S0022 - 1139 ( 00 ) 82652 - 4. Novak, M. ; Roth, A. ; Levine, M. ( 1988 ). `` Calcium oxalate retinopathy associated with methoxyflurane abuse ''. Retina ( Philadelphia, Pa. ). 8 ( 4 ) : 230 -- 236. doi : 10.1097 / 00006982 - 198808040 - 00002. PMID 3231916. National Institute for Occupational Safety and Health. Pocket guide to chemical hazards, methoxyflurane. Publication number 2005 - 149. Rosen, M. ; Latto, P. ; Asscher, A. ( 1972 ). `` Kidney function after methoxyflurane analgesia during labour ''. British Medical Journal. 1 ( 5792 ) : 81 -- 83. doi : 10.1136 / bmj. 1.5792. 81. PMC 1789263. PMID 5007074. Rosen, M. ; Mushin, W. ; Jones, P. ; Jones, E. ( 1969 ). `` Field trial of methoxyflurane, nitrous oxide, and trichloroethylene as obstetric analgesics ''. British Medical Journal. 3 ( 5665 ) : 263 -- 267. doi : 10.1136 / bmj. 3.5665. 263. PMC 1984095. PMID 4895340. Toomath, R. ; Morrison, R. ( 1987 ). `` Renal failure following methoxyflurane analgesia ''. The New Zealand medical journal. 100 ( 836 ) : 707 -- 708. PMID 3452163. External links Sheffield Museum of Anaesthesia : the Analgizer Medical Developments International Limited : Penthrox ( methoxyflurane ) Centers for Disease Control and Prevention : NIOSH Pocket Guide to Chemical Hazards General anesthetics ( N01A ) Inhalational Chloroethane ( ethyl chloride ) Chloroform Cyclopropane Desflurane Diethyl ether Enflurane Ethylene Fluroxene Halothane Isoflurane Methoxyflurane Methoxypropane Nitrous oxide Sevoflurane Trichloroethylene Vinyl ether Xenon Injection Phenols Fospropofol Propofol Opioids Morphine Oxycodone Anileridine Embutramide Fentanyl Alfentanil Phenoperidine Remifentanil ÷ Sufentanil Arylcyclohexylamines Esketamine Ketamine Phencyclidine Tiletamine Neuroactive steroids Alfadolone Alfaxalone Hydroxydione Others Propanidid WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III Analgesics ( N02A, N02B ) Opioids Opiates / opium Codeine ( + paracetamol, + aspirin ) Morphine ( + naltrexone ) Opium Laudanum Paregoric Semisynthetic Acetyldihydrocodeine Benzylmorphine Buprenorphine ( + naloxone ) Desomorphine Diamorphine ( heroin ) Dihydrocodeine ( + paracetamol ) Dihydromorphine Ethylmorphine Hydrocodone ( + paracetamol, + ibuprofen, + aspirin ) Hydromorphinol Hydromorphone Nicocodeine Nicodicodeine Nicomorphine Oxycodone ( + paracetamol, + aspirin, + ibuprofen, + naloxone, + naltrexone ) Oxymorphone Thebacon Synthetic Alfentanil Alphaprodine Anileridine Butorphanol Carfentanil Dextromoramide Dextropropoxyphene Dezocine Fentanyl ( + fluanisone ) Ketobemidone Levorphanol Lofentanil Meptazinol Methadone Nalbuphine NFEPP Pentazocine Pethidine ( meperidine ) Phenadoxone Phenazocine Piminodine Piritramide Propiram Remifentanil Sufentanil Tapentadol Tilidine Tramadol Paracetamol - type Acetanilide Bucetin Butacetin Paracetamol ( acetaminophen ) Parapropamol Phenacetin Propacetamol NSAIDs Propionates Fenoprofen Flurbiprofen Ibuprofen Ketoprofen Naproxen Oxaprozin Oxicams Meloxicam Piroxicam Acetates Diclofenac Indometacin Ketorolac Nabumetone Sulindac Tolmetin COX - 2 inhibitors Celecoxib Etoricoxib Lumiracoxib Parecoxib Rofecoxib Valdecoxib Fenamates Meclofenamic acid Mefenamic acid Salicylates Aspirin ( acetylsalicylic acid ) ( + paracetamol / caffeine ) Benorylate Diflunisal Ethenzamide Magnesium salicylate Salicin Salicylamide Salsalate Wintergreen ( methyl salicylate ) Pyrazolones Aminophenazone Ampyrone Metamizole ( dipyrone ) Nifenazone Phenazone Propyphenazone ( + paracetamol / caffeine ) Others Glafenine Cannabinoids Cannabidiol Cannabis Nabilone Nabiximols Tetrahydrocannabinol ( dronabinol ) Ion channel modulators Calcium blockers Gabapentin Gabapentin enacarbil Pregabalin Ziconotide Sodium blockers Carbamazepine Lacosamide Local anesthetics ( e.g., cocaine, lidocaine ) Mexiletine Nefopam Tricyclic antidepressants ( e.g., amitriptyline ) Na 1.7 / 1.8 - selective : DSP - 2230 Funapide PF - 05089771 Raxatrigine Potassium openers Flupirtine Myorelaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Mephenoxalone Methocarbamol Orphenadrine Others Analgesic adjuvant Analgecine Camphor Capsaicin Clonidine Ketamine Menthol Methoxyflurane Nefopam Proglumide Tricyclic antidepressants ( e.g., amitriptyline ) WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III Pharmacodynamics GABA receptor positive modulators Alcohols Brometone Butanol Chloralodol Chlorobutanol ( cloretone ) Ethanol ( alcohol ) ( alcoholic drink ) Ethchlorvynol Isobutanol Isopropanol Menthol Methanol Methylpentynol Pentanol Petrichloral Propanol tert - Butanol ( 2M2P ) tert - Pentanol ( 2M2B ) Tribromoethanol Trichloroethanol Triclofos Trifluoroethanol Barbiturates ( - ) - DMBB Allobarbital Alphenal Amobarbital Aprobarbital Barbexaclone Barbital Benzobarbital Benzylbutylbarbiturate Brallobarbital Brophebarbital Butabarbital / Secbutabarbital Butalbital Buthalital Butobarbital Butallylonal Carbubarb Crotylbarbital Cyclobarbital Cyclopentobarbital Difebarbamate Enallylpropymal Ethallobarbital Eterobarb Febarbamate Heptabarb Heptobarbital Hexethal Hexobarbital Metharbital Methitural Methohexital Methylphenobarbital Narcobarbital Nealbarbital Pentobarbital Phenallymal Phenobarbital Phetharbital Primidone Probarbital Propallylonal Propylbarbital Proxibarbital Reposal Secobarbital Sigmodal Spirobarbital Talbutal Tetrabamate Tetrabarbital Thialbarbital Thiamylal Thiobarbital Thiobutabarbital Thiopental Thiotetrabarbital Valofane Vinbarbital Vinylbital Benzodiazepines 2 - Oxoquazepam 3 - Hydroxyphenazepam Adinazolam Alprazolam Arfendazam Avizafone Bentazepam Bretazenil Bromazepam Brotizolam Camazepam Carburazepam Chlordiazepoxide Ciclotizolam Cinazepam Cinolazepam Clazolam Climazolam Clobazam Clonazepam Clonazolam Cloniprazepam Clorazepate Clotiazepam Cloxazolam CP - 1414S Cyprazepam Delorazepam Demoxepam Diazepam Diclazepam Doxefazepam Elfazepam Estazolam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Etizolam EVT - 201 FG - 8205 Fletazepam Flubromazepam Flubromazolam Fludiazepam Flunitrazepam Flunitrazolam Flurazepam Flutazolam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Haloxazolam Iclazepam Imidazenil Irazepine Ketazolam Lofendazam Lopirazepam Loprazolam Lorazepam Lormetazepam Meclonazepam Medazepam Menitrazepam Metaclazepam Mexazolam Midazolam Motrazepam N - Desalkylflurazepam Nifoxipam Nimetazepam Nitrazepam Nitrazepate Nitrazolam Nordazepam Nortetrazepam Oxazepam Oxazolam Phenazepam Pinazepam Pivoxazepam Prazepam Premazepam Proflazepam Pyrazolam QH - II - 66 Quazepam Reclazepam Remimazolam Rilmazafone Ripazepam Ro48 - 6791 Ro48 - 8684 SH - 053 - R - CH3 - 2 ′ F Sulazepam Temazepam Tetrazepam Tolufazepam Triazolam Triflubazam Triflunordazepam ( Ro5 - 2904 ) Tuclazepam Uldazepam Zapizolam Zolazepam Zomebazam Carbamates Carisbamate Carisoprodol Clocental Cyclarbamate Difebarbamate Emylcamate Ethinamate Febarbamate Felbamate Hexapropymate Lorbamate Mebutamate Meprobamate Nisobamate Pentabamate Phenprobamate Procymate Styramate Tetrabamate Tybamate Flavonoids 6 - Methylapigenin Ampelopsin ( dihydromyricetin ) Apigenin Baicalein Baicalin Catechin EGC EGCG Hispidulin Linarin Luteolin Rc - OMe Skullcap constituents ( e.g., baicalin ) Wogonin Imidazoles Etomidate Metomidate Propoxate Kava constituents 10 - Methoxyyangonin 11 - Methoxyyangonin 11 - Hydroxyyangonin Desmethoxyyangonin 11 - Methoxy - 12 - hydroxydehydrokavain 7, 8 - Dihydroyangonin Kavain 5 - Hydroxykavain 5, 6 - Dihydroyangonin 7, 8 - Dihydrokavain 5, 6, 7, 8 - Tetrahydroyangonin 5, 6 - Dehydromethysticin Methysticin 7, 8 - Dihydromethysticin Yangonin Monoureides Acecarbromal Apronal ( apronalide ) Bromisoval Carbromal Capuride Ectylurea Neuroactive steroids Acebrochol Allopregnanolone ( brexanolone ) Alfadolone Alfaxalone 3α - Androstanediol Androstenol Androsterone Certain anabolic - androgenic steroids Cholesterol DHDOC 3α - DHP 5α - DHP 5β - DHP DHT Etiocholanolone Ganaxolone Hydroxydione Minaxolone ORG - 20599 ORG - 21465 P1 - 185 Pregnanolone ( eltanolone ) Progesterone Renanolone SAGE - 105 SAGE - 217 SAGE - 324 SAGE - 516 SAGE - 689 SAGE - 872 Testosterone THDOC Nonbenzodiazepines β - Carbolines : Abecarnil Gedocarnil Harmane SL - 651,498 ZK - 93423 Cyclopyrrolones : Eszopiclone Pagoclone Pazinaclone Suproclone Suriclone Zopiclone Imidazopyridines : Alpidem DS - 1 Necopidem Saripidem Zolpidem Pyrazolopyrimidines : Divaplon Fasiplon Indiplon Lorediplon Ocinaplon Panadiplon Taniplon Zaleplon Others : Adipiplon CGS - 8216 CGS - 9896 CGS - 13767 CGS - 20625 CL - 218,872 CP - 615,003 CTP - 354 ELB - 139 GBLD - 345 Imepitoin JM - 1232 L - 838,417 Lirequinil ( Ro41 - 3696 ) NS - 2664 NS - 2710 NS - 11394 Pipequaline ROD - 188 RWJ - 51204 SB - 205,384 SX - 3228 TGSC01AA TP - 003 TPA - 023 TP - 13 U-89843A U-90042 Viqualine Y - 23684 Phenols Fospropofol Propofol Thymol Piperidinediones Glutethimide Methyprylon Piperidione Pyrithyldione Pyrazolopyridines Cartazolate Etazolate ICI - 190,622 Tracazolate Quinazolinones Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL - 164 Volatiles / gases Acetone Acetophenone Acetylglycinamide chloral hydrate Aliflurane Benzene Butane Butylene Centalun Chloral Chloral betaine Chloral hydrate Chloroform Cryofluorane Desflurane Dichloralphenazone Dichloromethane Diethyl ether Enflurane Ethyl chloride Ethylene Fluroxene Gasoline Halopropane Halothane Isoflurane Kerosine Methoxyflurane Methoxypropane Nitric oxide Nitrogen Nitrous oxide Norflurane Paraldehyde Propane Propylene Roflurane Sevoflurane Synthane Teflurane Toluene Trichloroethane ( methyl chloroform ) Trichloroethylene Vinyl ether Others / unsorted 3 - Hydroxybutanal α - EMTBL AA - 29504 Avermectins ( e.g., ivermectin ) Bromide compounds ( e.g., lithium bromide, potassium bromide, sodium bromide ) Carbamazepine Chloralose Chlormezanone Clomethiazole DEABL Dihydroergolines ( e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid ( dihydroergotoxine ) ) DS2 Efavirenz Etazepine Etifoxine Fenamates ( e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid ) Fluoxetine Flupirtine Hopantenic acid Lanthanum Lavender oil Lignans ( e.g., 4 - O - methylhonokiol, honokiol, magnolol, obovatol ) Loreclezole Menthyl isovalerate ( validolum ) Monastrol Niacin Nicotinamide ( niacinamide ) Org 25,435 Phenytoin Propanidid Retigabine ( ezogabine ) Safranal Seproxetine Stiripentol Sulfonylalkanes ( e.g., sulfonmethane ( sulfonal ), tetronal, trional ) Terpenoids ( e.g., borneol ) Topiramate Valerian constituents ( e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol ) Unsorted benzodiazepine site positive modulators : α - Pinene MRK - 409 ( MK - 0343 ) TCS - 1105 TCS - 1205 See also : Receptor / signaling modulators GABA receptor modulators GABA metabolism / transport modulators Glycine receptor modulators Receptor ( ligands ) GlyR Agonists : β - Alanine β - ABA ( BABA ) β - AIBA Caesium D - Alanine D - Serine GABA Glycine Hypotaurine Ivermectin L - Alanine L - Proline L - Serine L - Threonine MDL - 27531 Milacemide Picolinic acid Propofol Quisqualamine Sarcosine Taurine Positive modulators : Alcohols ( e.g., brometone, chlorobutanol ( chloretone ), ethanol ( alcohol ), tert - butanol ( 2M2P ), tribromoethanol, trichloroethanol, trifluoroethanol ) Alkylbenzene sulfonate Anandamide Barbiturates ( e.g., pentobarbital, sodium thiopental ) Chlormethiazole D12 - 116 Dihydropyridines ( e.g., nicardipine ) Etomidate Ginseng constituents ( e.g., ginsenosides ( e.g., ginsenoside - Rf ) ) Glutamic acid ( glutamate ) Ivermectin Ketamine Neuroactive steroids ( e.g., alfaxolone, pregnenolone ( eltanolone ), pregnenolone acetate, minaxolone, ORG - 20599 ) Nitrous oxide Penicillin G Propofol Tamoxifen Tetrahydrocannabinol Triclofos Tropeines ( e.g., atropine, bemesetron, cocaine, LY - 278584, tropisetron, zatosetron ) Volatiles / gases ( e.g., chloral hydrate, chloroform, desflurane, diethyl ether ( ether ), enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, toluene, trichloroethane ( methyl chloroform ), trichloroethylene ) Xenon Zinc Antagonists : 2 - Aminostrychnine 2 - Nitrostrychnine 4 - Phenyl - 4 - formyl - N - methylpiperidine αEMBTL Bicuculline Brucine Cacotheline Caffeine Colchicine Colubrine Cyanotriphenylborate Dendrobine Diaboline Endocannabinoids ( e.g., 2 - AG, anandamide ( AEA ) ) Gaboxadol ( THIP ) Gelsemine iso - THAZ Isobutyric acid Isonipecotic acid Isostrychnine Laudanosine N - Methylbicuculline N - Methylstrychnine N, N - Dimethylmuscimol Nipecotic acid Pitrazepin Pseudostrychnine Quinolines ( e.g., 4 - hydroxyquinoline, 4 - hydroxyquinoline - 3 - carboxylic acid, 5, 7 - CIQA, 7 - CIQ, 7 - TFQ, 7 - TFQA ) RU - 5135 Sinomenine Strychnine Thiocolchicoside Tutin Negative modulators : Amiloride Benzodiazepines ( e.g., bromazepam, clonazepam, diazepam, flunitrazepam, flurazepam ) Corymine Cyanotriphenylborate Daidzein Dihydropyridines ( e.g., nicardipine, nifedipine, nitrendipine ) Furosemide Genistein Ginkgo constituents ( e.g., bilobalide, ginkgolides ( e.g., ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M ) ) Imipramine NBQX Neuroactive steroids ( e.g., 3α - androsterone sulfate, 3β - androsterone sulfate, deoxycorticosterone, DHEA sulfate, pregnenolone sulfate, progesterone ) Opioids ( e.g., codeine, dextromethorphan, dextrorphan, levomethadone, levorphanol, morphine, oripavine, pethidine, thebaine ) Picrotoxin ( i.e., picrotin and picrotoxinin ) PMBA Riluzole Tropeines ( e.g., bemesetron, LY - 278584, tropisetron, zatosetron ) Verapamil Zinc NMDAR See here instead. Transporter ( blockers ) GlyT1 ACPPB ALX - 1393 ALX - 5407 ( NFPS ) AMG - 747 ASP2535 Bitopertin ( RG1678 / RO4917838 ) CP - 802079 Ethanol ( alcohol ) Glycyldodecylamide GSK1018921 LY - 2365109 ORG - 24598 ORG - 25935 ( SCH - 900435 ) PF - 02545920 PF - 03463275 PF - 04958242 Sarcosine SSR - 103,800 SSR - 504,734 GlyT2 Amoxapine Ethanol ( alcohol ) NAGly Opiranserin ( VVZ - 149 ) ORG - 25543 VVZ - 368 See also Receptor / signaling modulators GABA receptor modulators GABA receptor positive modulators Ionotropic glutamate receptor modulators Ionotropic glutamate receptor modulators AMPAR Agonists : Main site agonists : 5 - Fluorowillardiine Acromelic acid ( acromelate ) AMPA BOAA Domoic acid Glutamate Ibotenic acid Proline Quisqualic acid Willardiine ; Positive allosteric modulators : Aniracetam Cyclothiazide CX - 516 CX - 546 CX - 614 Farampator ( CX - 691, ORG - 24448 ) CX - 717 CX - 1739 CX - 1942 Diazoxide Hydrochlorothiazide ( HCTZ ) IDRA - 21 LY - 392098 LY - 395153 LY - 404187 LY - 451646 LY - 503430 Mibampator ( LY - 451395 ) Nooglutyl ORG - 26576 Oxiracetam PEPA PF - 04958242 Piracetam Pramiracetam S - 18986 Tulrampator ( S - 47445, CX - 1632 ) Antagonists : ACEA - 1011 ATPO Becampanel Caroverine CNQX Dasolampanel DNQX Fanapanel ( MPQX ) GAMS Kaitocephalin Kynurenic acid Kynurenine Licostinel ( ACEA - 1021 ) NBQX PNQX Selurampanel Tezampanel Theanine Topiramate YM90K Zonampanel ; Negative allosteric modulators : Barbiturates ( e.g., pentobarbital, sodium thiopental ) Cyclopropane Enflurane Ethanol ( alcohol ) Evans blue GYKI - 52466 GYKI - 53655 Halothane Irampanel Isoflurane Perampanel Pregnenolone sulfate Sevoflurane Talampanel ; Unknown / unsorted antagonists : Minocycline KAR Agonists : Main site agonists : 5 - Bromowillardiine 5 - Iodowillardiine Acromelic acid ( acromelate ) AMPA ATPA Domoic acid Glutamate Ibotenic acid Kainic acid LY - 339434 Proline Quisqualic acid SYM - 2081 ; Positive allosteric modulators : Cyclothiazide Diazoxide Enflurane Halothane Isoflurane Antagonists : ACEA - 1011 CNQX Dasolampanel DNQX GAMS Kaitocephalin Kynurenic acid Licostinel ( ACEA - 1021 ) LY - 382884 NBQX NS102 Selurampanel Tezampanel Theanine Topiramate UBP - 302 ; Negative allosteric modulators : Barbiturates ( e.g., pentobarbital, sodium thiopental ) Enflurane Ethanol ( alcohol ) Evans blue NS - 3763 Pregnenolone sulfate NMDAR Agonists : Main site agonists : AMAA Aspartate Glutamate Homocysteic acid ( L - HCA ) Homoquinolinic acid Ibotenic acid NMDA Proline Quinolinic acid Tetrazolylglycine Theanine ; Glycine site agonists : β - Fluoro - D - alanine ACBD ACC ( ACPC ) ACPD AK - 51 Apimostinel ( NRX - 1074 ) B6B21 CCG D - Alanine D - Cycloserine D - Serine DHPG Dimethylglycine Glycine HA - 966 L - 687414 L - Alanine L - Serine Milacemide Neboglamine ( nebostinel ) Rapastinel ( GLYX - 13 ) Sarcosine ; Polyamine site agonists : Neomycin Spermidine Spermine ; Other positive allosteric modulators : 24S - Hydroxycholesterol DHEA ( prasterone ) DHEA sulfate ( prasterone sulfate ) Epipregnanolone sulfate Pregnenolone sulfate SAGE - 201 SAGE - 301 SAGE - 718 Antagonists : Competitive antagonists : AP5 ( APV ) AP7 CGP - 37849 CGP - 39551 CGP - 39653 CGP - 40116 CGS - 19755 CPP Kaitocephalin LY - 233053 LY - 235959 LY - 274614 MDL - 100453 Midafotel ( d - CPPene ) NPC - 12626 NPC - 17742 PBPD PEAQX Perzinfotel PPDA SDZ - 220581 Selfotel ; Glycine site antagonists : 4 - Cl - KYN ( AV - 101 ) 5, 7 - DCKA 7 - CKA ACC ACEA - 1011 ACEA - 1328 Apimostinel ( NRX - 1074 ) AV - 101 Carisoprodol CGP - 39653 CNQX D - Cycloserine DNQX Felbamate Gavestinel GV - 196771 Harkoseride Kynurenic acid Kynurenine L - 689560 L - 701324 Licostinel ( ACEA - 1021 ) LU - 73068 MDL - 105519 Meprobamate MRZ 2 / 576 PNQX Rapastinel ( GLYX - 13 ) ZD - 9379 ; Polyamine site antagonists : Arcaine Co 101676 Diaminopropane Diethylenetriamine Huperzine A Putrescine ; Uncompetitive pore blockers ( mostly dizocilpine site ) : 2 - MDP 3 - HO - PCP 3 - MeO - PCE 3 - MeO - PCMo 3 - MeO - PCP 4 - MeO - PCP 8A - PDHQ 18 - MC α - Endopsychosin Alaproclate Alazocine ( SKF - 10047 ) Amantadine Aptiganel Argiotoxin - 636 Arketamine ARL - 12495 ARL - 15896 - AR ARL - 16247 Budipine Coronaridine Delucemine ( NPS - 1506 ) Dexoxadrol Dextrallorphan Dextromethadone Dextromethorphan Dextrorphan Dieticyclidine Diphenidine Dizocilpine Ephenidine Esketamine Etoxadrol Eticyclidine Fluorolintane Gacyclidine Ibogaine Ibogamine Indantadol Ketamine Ketobemidone Lanicemine Levomethadone Levomethorphan Levomilnacipran Levorphanol Loperamide Memantine Methadone Methorphan Methoxetamine Methoxphenidine Milnacipran Morphanol NEFA Neramexane Nitromemantine Noribogaine Norketamine Orphenadrine PCPr PD - 137889 Pethidine ( meperidine ) Phencyclamine Phencyclidine Propoxyphene Remacemide Rhynchophylline Rimantadine Rolicyclidine Sabeluzole Tabernanthine Tenocyclidine Tiletamine Tramadol ; Ifenprodil ( NR2B ) site antagonists : Besonprodil Buphenine ( nylidrin ) CO-101244 ( PD - 174494 ) Eliprodil Haloperidol Isoxsuprine Radiprodil ( RGH - 896 ) Rislenemdaz ( CERC - 301, MK - 0657 ) Ro 8 - 4304 Ro 25 - 6981 Safaprodil Traxoprodil ( CP - 101606 ) ; NR2A - selective antagonists : MPX - 004 MPX - 007 TCN - 201 TCN - 213 ; Cations : Hydrogen Magnesium Zinc ; Alcohols / volatile anesthetics / related : Benzene Butane Chloroform Cyclopropane Desflurane Diethyl ether Enflurane Ethanol ( alcohol ) Halothane Hexanol Isoflurane Methoxyflurane Nitrous oxide Octanol Sevoflurane Toluene Trichloroethane Trichloroethanol Trichloroethylene Urethane Xenon Xylene ; Unknown / unsorted antagonists : ARR - 15896 Bumetanide Caroverine D - αAA Dexanabinol Flufenamic acid Flupirtine FPL - 12495 FR - 115427 Furosemide Hodgkinsine Ipenoxazone ( MLV - 6976 ) MDL - 27266 Metaphit Minocycline MPEP Niflumic acid Pentamidine Pentamidine isethionate Piretanide Psychotridine Transcrocetin ( saffron ) See also : Receptor / signaling modulators Metabotropic glutamate receptor modulators Glutamate metabolism / transport modulators Retrieved from `` https://en.wikipedia.org/w/index.php?title=Methoxyflurane&oldid=822507323 '' Categories : Organofluorides Organochlorides Analgesics Ethers General anesthetics GABAA receptor positive allosteric modulators Glycine receptor agonists NMDA receptor antagonists Fluranes Hidden categories : CS1 maint : Multiple names : authors list Good articles Articles with changed EBI identifier ECHA InfoCard ID from Wikidata Drugboxes which contain changes to verified fields Drugboxes which contain changes to watched fields Talk Contents About Wikipedia تۆرکجه Deutsch فارسی Français Italiano Português Русский Српски / srpski Srpskohrvatski / српскохрватски Suomi Українська 中文 4 more Edit links This page was last edited on 26 January 2018, at 19 : 43. 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Question: what's in the green whistles on bondi rescue
Answer: Methoxyflurane