A comparative investigation in the rat of the anesthetic effects of the isomers of two barbiturates.

The sensitivities in the brain of the barbiturates N-methyl-cyclobarbital (MCB) and hexobarbital (HEX) were determined by an anesthesia threshold in male rats. The criterion was a burst suppression in the EEG of 1 s or more (the 'silent second'). The dose needed to induce the criterion was used as the threshold. Available for testing were with MCB the isomers and the racemate and with HEX the isomers and various combinations of them. In experiment 1 the 4 isomers and the racemates were all tested in the same group of animals. In experiment 2 various combinations of HEX were tested. With HEX the (+)-S-isomer and with MCB the (-)-R-isomer was the most potent one. The differences in anesthetic action between the isomers were largest with HEX. During induction of anesthesia no jerks were recorded with (-)-R-MCB. All the other isomers induced jerks. The only significant regression found, when all isomers were tested against each other, was a negative one between (-)-R-MCB and (-)-R-HEX (r = -0.79). No significant relations were found between the isomers and the corresponding racemate. Experiments with the racemate of MCB and with various combinations of the isomers of HEX indicated that a potentiation appeared when the isomers were used together.