The effects of amines on oxidations of the brain

AN investigation into the effects of narcotics on the oxidative processes of the brain has shown [Quastel and Wheatley, 1932, 1, 2] that these substances exert specific inhibitions at low concentrations. The oxidations of glucose, sodium lactate and sodium pyruvate are markedly affected whilst those of sodium succinate and p-phenylenediamine are unimpaired. This generalisation holds for all narcotics investigated, the inhibitory power varying, among narcotics of the same chemical type, with the hypnotic activity. A view of the mechanism of narcosis, which fits the observed facts, is that the narcotic is adsorbed from the blood-stream at a specific area or centre of the nervous system. Here it diminishes the ability of the cells constituting the nervous centre to activate lactic or pyruvic acid and in this way inhibits the oxidation by these cells of glucose, lactic or pyruvic acid. The activation and access of oxygen remain unimpaired, but, in consequence of the inhibition of oxidative powers, a lowered amount of energy is available to the narcotised nervous centre for the accom- plishment of its functional activity. Narcosis-or a depression of the normal activity of the centre in question-may then ensue. In spite therefore of the fact that oxygen is freely available, a state equivalent to partial anoxaemia exists at those areas of the nervous centre where the narcotic is adsorbed. The results of experiments carried out under anaerobic conditions (oxygen being replaced by methylene blue) show that the adsorption of the narcotic is re- versible, a competition taking place between lactic acid and the narcotic for possession of the active surfaces in the nervous centre [Davies and Quastel, 1932].