Blood concentration and urinary excretion data demonstrated that subjects who had ingested 1 g of paracetamol after fasting overnight absorbed the drug up to 5 times more rapidly but to the same extent as when they ingested the drug after a substantial high carbohydrate breakfast. Subjects who had ingested 1 g of paracetamol immediately before sleep at night excreted up to 36% less than when they took the drug at 8.30 a.m.

The rates of rearrangement of several aminochromes have been measured in: (I) water, (2) aqueous sodium hydroxide, and (3) aqueous zinc acetate. The rates were found t o be first order with respect to aminochrome concentration in each reaction medium, and to zinc acetate concentration. However, no simple kinetic relationship between the rate of rearrangement and alkali concentration was detected. The rate increased very rapidly with increasing alkali concentration.Mechanisms for these rearrangements are suggested, based on the influence of substituents in the I-. 2-, and 3-positions of the aminochrome molecule on the kinetic and thermodvnamic features of the reaction.

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The reaction between adrenochrome and glutathione has been studied. 'The main products result from the 1,4-addition of glutathione to the Cg unsaturated carbonyl systetns in adrenochrome involving the c6-C~ and the c4-c~~ double bonds, and are probably 7-S-glutathionyl-5,6-dihydroxy-N-methylindole and 9-S-glutathionyl-2,3,6,9-tetrahydro-3,5-dihydroxy-6-0~0-N-methylindole respectively. 5,6-Dihydroxy-N-methylindole is also formed during the interaction of glutathione and adrenochrome. The lnechanisrns by which these compounds are formed are discussed.

The mechanism of the reduction of adrenochrome by ascorbic acid in water and methanol has been investigated. The rate of reduction is directly dependent on the concentration of adrenochrome; rates of reduction in methanol are also first-order with respect to the ascorbic acid concentration. At the lowest concentration of ascorbic acid used the reductions in methanol are more rapid than similar reductions in water using the same total ascorbic acid concentration, However, reactions in water do show a first-order dependence on the concentration of the fraction of undissociated ascorbic acid present. Addition of dehydroascorbic acid to these reactions in methanol decreases the rate of reduction while there is an increase when dehydroascorbic acid is added to the reductions in water. A mechanism for the reduction of adrenochrome by ascorbic acid is proposed.* The 2,3-dihydroindole-5,6-quinones (obtained by the oxidative cyclisation of catecholamines) are known as the '' aminochromes." The physical and chemical properties of adrenochrome, which is a typical aminochrome, suggest that the zwitterionic form of the molecule makes the major contribution t o the adrenochrome structure.