The effect of depressants on the metabolism of stimulated cerebral tissues

Depression of the activity of the central nervous system by agents such as barbiturates* is accompanied by metabolic changes in the brain itself.The changes include a fall in respiration, lactic acid, and inorganic phosphate and a rise in phosphocreatine.In investigating the action of depressants, various attempts have been made to reproduce these changes under conditions simpler than those of the whole animal.The metabolic characteristics named can all be measured in cerebral tissues in vitro.However, none of the changes brought about in them by depressants in vivo has yet been unequivocally reproduced in cerebral tissues in vitro by con- centrations of the depressants used therapeutically.Thus, when change occurs in the aerobic formation of lactic acid, it is in opposite senses under the two conditions.It is unchanged or increased in vitro by a barbiturate (Hutchinson & Stotz, 1941), by chloral and butobarbitone (Buchel & Mcllwain, 1950a, b; Rosenberg, Buchel, Etling & Levy, 1950) and by pentobarbitone, amylobarbitone, chloretone, tribromoethanol and phenobarbitone (Webb & Elliott, 1951).It is decreased in vivo by phenobarbitone, pentobarbitone, amylobarbitone and ether (Stone, 1938; Richter & Dawson, 1948).Phosphocreatine in the tissue also changes in opposite senses in vivo and in vitro.It is raised in vivo during the action of pentobarbitone (LePage, 1946; Dawson & Richter, 1950), but falls in vitro during the action of butobarbitone, allobarbitone, and chloral (Buchel & Mcllwain, 1950a, b).Simi- larly opposed changes take place in the inorganic phosphate of the tissue (Buchel & Mcllwain, 1950a, b).Observations on respiration come closest to showing parallelism in vivo and in vitro.They have constituted a large proportion of biochemical work on narcotic action since the demonstration by Warburg (1910) (see also Minami, 1923) that such substances can inhibit respiration.Concentrations of depressants higher than those used therapeutic-* The following trivial names are used: butobarbitone for 5-butyl-5-ethylbarbituric acid (Soneryl); pentobarbitone for 5-ethyl-5-(l-methylbutyl) barbituric acid; amylobarbitone for 5-ethyl-5-(3-methylbutyl) barbituric acid (Amytal); phenobarbitone for 5-ethyl-5-phenylbarbituric acid; allo- barbitone for 5:5-diallylbarbituric acid (Dial).