Tierexperimentelle Untersuchungen über den Mechanismus der narkoseverkürzenden Wirkung von Monoaminoxydase-Hemmstoffen

Abstract

The monoamine oxidase (MAO) inhibitors nialamide and iproniazid, injected 20 to 60 hours before the injection of the anesthetic, shorten hexobarbital anesthesia in mice. This effect is not produced by all MAO inhibitors. MO 911 and SKF 385, like nialamide and iproniazid, produce an irreversible inhibition of MAO and also an accumulation of amines in the brain. During this time they do not influence the duration of hexobarbital anesthesia. The shortening of the duration of narcosis produced by nialamide and iproniazid occurs even when the accumulation of amines in the brain is prevented by pretreatment with harmaline. These results indicate that there is probably no relationship between the shortening of anesthesia and the accumulation of amines in the brain. Shortly after the injection of nialamide or iproniazid, the breakdown of hexobarbital by the microsomal enzymes of the liver is inhibited, but is increased 48 hours later at which time it could produce a shortening of the duration of anesthesia. Twenty to 24 hours after injecting these MAO inhibitors the hepatic breakdown of hexobarbital is still unchanged or even slightly inhibited and yet the duration of hexobarbital anesthesia is already significantly shortened. The shortening of the duration of anesthesia in the presence of normal hepatic breakdown of hexobarbital is not specific for MAO inhibitors. It can also be seen after an injection of SKF 525 A which is not a MAO inhibitor. The shortening of the duration of narcosis produced by nialamide and iproniazid must be due to a mechanism independant of both MAO inhibition and hexobarbital breakdown by the liver. To explain this shortening one could suggest a decreased penetration of the anesthetic into the brain or an increased elimination from the brain.