THE RELATIONSHIP BETWEEN CHEMICAL STRUCTURE AND INHIBITORY ACTION OF BARBITURIC ACID DERIVATIVES ON RAT BRAIN RESPIRATION IN VITRO

¹ From the Department of Physiology, Stanford University, California

1. The effects of graded concentrations of three groups of substituted barbituric acid derivatives on the respiration of rat cerebral cortex slices were described. Group I consisted on an homologous series of six 5-alkyl-5-ethyl barbiturates in which the alkyl substitution ranged from the ethyl to the hexyl group. Group II was composed of an homologous series of three 5-allyl-5-alkyl derivatives in which the alkyl groups were isopropyl, isobutyl and 1-methylbutyl respectively. Group III was miscellaneous, consisting of two cyclic derivatives and one thiobarbiturate. The data were presented in the form of concentration-action curves.

2. It was found that with increasing length of the alkyl sidechain in the compounds of groups I and II there was decrease in the molar concentration of the compound required in the suspension medium of the respirometer vessel to produce 50% inhibition of the oxygen consumption of rat cerebral cortex in vitro. Several other parallelisms between the physical properties and biological actions of these drugs were described from data in the literature.

3. The problem of the relationship between doses of these drugs inducing anesthesia in vivo and concentrations inhibiting brain respiration in vitro was discussed. It was pointed out that quantitative formulation of this relationship must await precise determination of the concentrations of the drugs in the brain, both in vivo and in vitro.