THE DELAY IN ONSET OF ACTION OF INTRAVENOUSLY INJECTED ANESTHETICS

¹ From the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

A delay occurs between the intravenous introduction of certain anesthetics and the full development of their action. The only drugs that I have found to have this property are chloraloses and 5,5-disubstituted derivatives of barbituric acid and hydantoin. The lags of a number of these drugs have been measured at doses designed to give comparable depths of anesthesia.

Among the eighteen 5,5-disubstituted barbituric acids studied, it has been demonstrated that anesthetic dose and lag are associated properties, the more active drugs tending to have more rapid onset of action.

This association might be explained if it were assumed that the delay is the time required for the drug to penetrate into or through the cell membrane, the more rapid penetration of the more active drugs being due to their greater relative solubility in the lipoids of the membrane.

This hypothesis is inadequate to explain the unequal rates of onset of the antipodal arabinochloraloses.

No reason is apparent for the fact that the property of slow onset of action is limited to those chemical classes named.