Benzedrine (β-phenylisopropylamine) and brain metabolism

Abstract

Respiration of slices of brain or minced brain in a glucose medium decreases in the presence of tyramine. [beta]-indolethylamine or isoamylamine. This decrease is neutralized by the presence of benzedrine ([alpha]-phenylisopropylamine sulphate). The same phenomenon obtains in the presence of tyramine when glucose is replaced by Na succinate. The effect is not due wholly to the amine itself but to a product of oxidation of the amine, i.e., either the corresponding aldehyde, or a product formed by further metabolism of the aldehyde. Succinate protects succinic dehydrogenase from the toxic influence of this product. Benzedrine owes its stimulating influence to its ability to compete reversibly with amines for the amine oxidase of brain and of other organs, thereby reducing the rate of formation of inhibitory aldehyde. l-Ephedrine and 3-methoxy-4-hydroxyphenylisopropylamine are much less active than benzedrine, and 3:4 methylenedioxyphenyliso-propylamine has about the same activity as benzedrine. The equilibrium constants of these amines with amine oxidase were detd. Aldehydes such as isovaleric aldehyde, and p-hydroxybenzaldehyde inhibit respiration of brain, and their inhibitory effects are not neutralized by the addition of benzedrine. Benzedrine has no retarding action on the decreases of respiration of brain tissue in a glucose medium due to the presence of luminal, chloretone or bulbocapnine. The possible clinical significance of these results is discussed. The relative stimulating actions of ephedrine, benzedrine, and benzedrine derivatives on brain respiration in the presence of tyramine parallel the relative stimulating actions of these substances on the c. n. s. as observed in vitro.