Diethyl ether
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Also known as etherTS
An industrial solvent which is sometimes used recreationally as a dissociative anaesthetic, with a short length of action. Effects are similar to alcohol. Leaves one's breath tasting and smelling strongly of ether for much longer than the experience lasts.TS
Mechanism of actionPH
The mechanism of action by which .... ethyl ether produce/s/ reversible loss of consciousness is still unclear. Anesthesia can be produced by a wide variety of chemical agents, ranging from inert rare gases to steriodal molecules. This apparent lack of specificity, together with the observation that general anesthesia can be reversed by high pressure, poses a unique pharmacological problem. Most theories concern interaction of anesthetics with either membrane lipids or hydrophobic regions of specificic membrane-bound proteins. One hypothesis is that the anesthetic changes the function of an ion channel protein by modifying the conformation of the protein. Some investigators suggest that the GABA receptor may be the ion channel protein that is affected by inhalation of anesthetic agents... The most appropriate concept for the mechanism of general anesthesia /may be/ a the heterogenous site of anesthetic action, including both lipid and protein membrane components linked with neuronal function.
In chronically catheterized rats, diethyl ether increased plasma adrenaline and noradrenaline concentrations indicating that this drug stimulates both neurosympathetic and adrenomedullary functions. These effects appear to be centrally mediated, since ganglionic blockade or spinal transection completely counteracted the diethyl ether induced increases in plasma calcium levels.
Hippocampal EEG signals derived from chronically implanted electrodes in the freely moving rat were recorded before and after administration of centrally acting drugs, and analyzed by power and coherence spectra. Diethyl ether induced a low frequency (3-6 c/s) theta power and coherence peak in the immobile rat, which was sensitive to atropine or scopolamine. The residue spectrum, defined as the EEG spectrum with the theta harmonics removed, was sensitive to centrally acting drugs. Diethyl ether suppressed fast waves of 50-100 c/s, and some conditions, enhanced 15-50 c/s waves.
The plasma beta-endorphin responses to ether and handling stress were examined in animals of various ages. At each age studied there was a significant, stress-induced elevation of plasma beta-endorphin-like immunoreactivity levels were higher in animals 3,7, and 14 days of age than in adults.
Cortical action potential activity is suppressed by ether anesthesia and is not affected when sensory fibers in the sciatic nerve are stimulated. Consequently, ether blocks sensory pathways to the cortex; the blockade occurs even before cortical activity is entirely suspended. In contrast, pentobarbital suppresses activity in the cortex without blocking the sensory path to it during sciatic nerve stimulation.
Pharmacokinetics
AbsorptionPH
After inhalation, ethyl ether is rapidly transferred from alveoli to blood. The normal alveolar membrane poses no barrier to the transfer of ethyl ether in either direction. The blood/gas distribution coefficient of ethyl ether is high - 12.1. For oil/gas, the distribution coefficient is 65. ...The penetration /of ethyl ether/ in rabbit skin /was studied/. ... Doses over 20 mL/kg bw could not be retained in contact with the skin. ... The single dermal penetration LD50 was greater than 20 mL/kg bw.
The majority of inhaled ethyl ether is excreted unchanged through the lungs. In experiments on dogs, /it was/ reported that the recovery of ethyl ether in expired air was 79-92% (average for 12 dogs 87%).
... Over 90% of it can be recovered in the exhaled air. A small fraction is excreted in the urine, milk, sweat and other body fluids, and a tiny amount escapes by diffusion through the intact skin. All volatile anesthetics easily pass placental barrier ...
Diethyl ether is instantaneously absorbed from inhaled air into the bloodstream, from which it passes rapidly into the brain. ... It is also taken up rapidly by fatty tissue in rats.
For more Absorption, Distribution and Excretion (Complete) data for DIETHYL ETHER (15 total), please visit the HSDB record page.
MetabolismPH
It has been estimated that about 8-10% of absorbed ethyl ether is metabolized in the body whereas the remainder is excreted unchanged through the lungs. Ethyl ether is metabolized to ethanol and acetaldehyde by the inducible hepatic microsomal enzyme system, a cytochrome P450-containing monooxygenase system. Ethanol and acetaldehyde are rapidly oxidized to acetate, and the acetate subsequently enters the 2-carbon pool of intermediary metabolism.
When (14)C diethyl ether ... admin ... to mice by inhalation a proportion was rapidly metabolized into palmitic, stearic, & oleic acids & cholesterol, which, together with 3 other non-volatile radioactive metab ... mono-, di-, & tri-glycerides, were recovered from liver.
Diethyl ether caused detectable blood acetaldehyde levels in 15 patients. Avg acetaldehyde concn was 21 umolar which approximates the level found after intake of ethanol.
Liver microsomes metabolized diethyl ether to acetaldehyde. The reaction was NADPH-dependent, & inhibited by CO & antibody to rat liver cytochrome P450. Cytochrome P450 containing monooxygenase system analogous to o-dealkylation is indicated.
For more Metabolism/Metabolites (Complete) data for DIETHYL ETHER (10 total), please visit the HSDB record page.
Diethyl ether can be absorbed following ingestion and inhalation, and is then rapidly distributed to the brain and fatty tissues. Diethyl ether is not metabolized in humans and is excreted mainly in expired air. (T36)
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.