Possible biochemical mechanism of the toxic effects of barbiturates

: Administration of amytal or phenobarbital to rats results in inhibition of liver respiration determined by oxygen uptake in isolated tissue preparations. Increasing doses of phenobarbital cause an increase of inhibition of liver respiration. In vitro addition of vitamin K3 to liver preparations from rat treated by amytal or administration of vitamin K3 after barbiturate-induced intoxication reverses the inhibition of respiration. It is also shown that the lethal effects of amytal are significantly lowered after administration of vitamin K3. It is concluded that the toxic effects of barbiturates are partially due to the inhibition of mitochondrial respiration at the level of NADH-dehydrogenase.