Preservation of Energy Compounds

Woodbury, Timiras and Vernadakis, Hormones, Brain Function, and Behavior (1957),⁴⁸³ reported that PHT increased glycogen in rat brain.

483. Woodbury, D. M., Timiras, P. S., and Vernadakis, A., Modification of adrenocartical function by centrally acting drugs and the influence of such modification on the central response to these drugs, Hormones, Brain Function, and Behavior, 38-50, H. Hoagland, Ed., Academic Press, New York, 1957.

Bernsohn, Possley and Custod, Pharmacologist (1960),¹⁷ demonstrated that PHT (25 mg/kg), two hours prior to measurement, more than doubled creatinine phosphate levels in rat brain. With control values of 3.30 µM/gm of brain, creatinine phosphate values were 1.30 for chlordiazepoxide, 4.40 for chlorpromazine, and 7.38 for PHT.

17. Bernsohn, L., Possley, L., and Custod, J. T., Alterations in brain adenine nucleotides and creatinine phosphate in vivo after the administration of chlorpromazine, JB-516, Dilantin and RO 5-0650 (Librium), Pharmacologist, 2: 67, 1960.

Broddle and Nelson, Federation Proceedings (1968),³⁷ found that PHT (50 mg/ kg) can decrease brain metabolic rate 40 to 60%, as well as increase the concentrations of brain energy compounds measured, i.e., phosphocreatine, serum and brain glucose and glycogen.

37. Broddle, W. D. and Nelson, S. R., The effect of diphenylhydantoin on energy reserve levels in brain, Fed. Proc., 27: 751, 1968.

Hutchins and Rogers, British Journal of Pharmacology (1970),⁷³⁹ found that PHT (20 mg/kg, intraperitoneally) increased the concentration of brain glycogen in mouse brain by 7% at 30 minutes and by 11% at 120 minutes.

739. Hutchins, D. A. and Rogers, K. J., Physiological and drug-induced changes in the glycogen content of mouse brain, Brit. J. Pharmacol., 39: 9-25, 1970.

Gilbert, Gray and Heaton, Biochemical Pharmacology (1971),¹⁰⁷¹ demonstrated that brain glucose levels were increased in mice who received PHT (20 mg/kg). The authors also found that PHT significantly increased the uptake of xylose by brain slices, without affecting glucose utilization by cerebral cortex slices. The authors concluded that PHT stimulates glucose transport into the brain. They considered the possibility that, with PHT, the extra glucose may play a role independent of its more obvious one as a substrate in oxidative metabolism, such as stabilization of water molecules in the cell membrane, with a consequent stabilizing effect on neuronal excitability.

1071. Gilbert, J. C., Gray, P., and Heaton, G. M., Anticonvulsant drugs and brain glucose, Biochem. Pharmacol., 20: 240-243, 1971.

Kogure, Scheinberg, Kishikawa and Busto , Dynamics of Brain Edema (1976),²²¹³ using a rat stroke model to study focal cerebral infarction, demonstrated that PHT (30 mg/kg, intraperitoneally), thirty minutes prior to stroke, preserved energy compounds and prevented the ischemia-induced rise of cyclic AMP in brain.

2213. Kogure, K., Scheinberg, R., Kishikawa, H. and Busto, R., The role of monoamines and cyclic AMP in ischemic brain edema, Dynamics of Brain Edema, Pappius, H. M. and Feindel, W., Eds., Springer, NY, 1976.

McCandless, Feusner, Lust and Passonneau , Journal of Neurochemistry (1979),²²²⁹ demonstrated that PHT (25 mg/ kg, intraperitoneally) counteracted the maximal electroshock-induced decreases in phosphocreatine, ATP, glucose and glycogen in mouse cerebellum.

2229. McCandless, D. W., Feussner, G. K., Lust, W. D. and Passonneau, J. V., Metabolite levels in brain following experimental seizures: the effects of maximal electroshock and phenytoin in cerebellar layers, J. Neurochem., 32: 743-53, 1979.

Advisory