EFFECTS OF MORPHINE AND ITS DERIVATIVES ON INTERMEDIARY METABOLISM I. THE INFLUENCE OF MORPHINE, CODEINE AND THEBAINE ON THE ACTIVITY OF SEVERAL DEHYDROGENASES AND ON THE RESPIRATION OF RAT CEREBRUM

¹ From the Department of Pharmacology, University of Wisconsin, Madison

The effects of morphine, codeine and thebaine on several dehydrogenases prepared from animal tissues, and on the oxygen uptake of various preparations of rat cerebrum, in the presence of certain added substrates, have been determined.

Lactic, citric and glucose dehydrogenases are inhibited by 0.06, 0.12 and 0.24 per cent morphine. Succinic and alcohol dehydrogenases are not affected. Neither codeine nor thebaine in concentrations of 0.06, 0.12 and 0.24 per cent has any significant effect on glucose, succinic, alcohol or citric dehydrogenases. Morphine, codeine and thebaine increase the rate of reduction of methylene blue by a phosphate extract of heart muscle.

Morphine (0.12 per cent) has no significant effect on the no-substrate oxygen uptake of cerebral cortex slices, cerebral mince, or washed, homogenized cerebrum of the albino rat. The oxygen uptake in the presence of added lactate is inhibited in all three preparations of cerebrum by 0.12 per cent morphine. The oxygen uptake of cerebrum in the presence of added glucose, pyruvate and -ketoglutarate is reduced by morphine in some preparations but not in others, whereas it is unaffected by morphine in the presence of added citrate, succinate, fumarate and malate.