The Anesthetic Properties of Certain Unsaturated Ethers.

From a general consideration of the chemo-pharmacological properties of di-ethyl ether and ethylene, especially in regard to their marked anesthetic power and relatively low toxicity, it seemed possible to predict that compounds combining the chemical characteristics of each would be interesting general anesthetic agents. This prediction might be made more specific by further reference to the theory of the relationship between chemical constitution and pharmacological action. In certain homologous series of absorbable aliphatic compounds (as the monohydric alcohols) toxicity increases (without a comparable increase in desired activity), in proportion to the number of carbon atoms in the straight carbon chain. Also related to chemical structure in such a series are certain anesthetically important physical properties, such as boiling points. So, one might venture to anticipate that the higher members of our proposed homologous series of unsaturated ethers would not be found as satisfactory inhalation anesthetic substances as the lower members of the series, because of too high boiling points and too great toxicity.

Through the kindness of Professor Sigmund Fraenkel of Vienna, we obtained vinyl-ethyl ether, allyl-ethyl ether, and di-allyl ether, and through the courtesy of Professor Lauder Jones of Princeton, we secured from Doctor Randolph Major di-vinyl ether, vinyl-ethyl ether, and isopropenyl-ethyl ether. These agents are all volatile colorless liquids with odors varying from the rather pleasant aromatic vapor of di-vinyl ether to the pungent irritation of the allyl compounds. Unfortunately only small quantities of these substances could be supplied (none in excess of 12 cc), so that only tentative determinations could be made of their partition coefficients and of their action on inhalation in mice.