Baskin, Leibman, De Witt, Orr, Tarzy, Levy, Krusz, Dhopesh and Schraeder, Neurology (1978),1735 examined platelet taurine levels, as a model for nerve-ending bio-chemistry, in epileptic patients. Patients whose seizures were controlled by PHT had significantly higher platelet taurine levels than patients not receiving PHT.

1735. Baskin, S. I., Leibman, A. J., DeWitt, W. S., Orr, P. L., Tarzy, N. T., Levy, P., Krusz, J. C., Dhopesh, V. P. and Schraeder, P. L., Mechanism of the anticonvulsant action of phenytoin: regulation of central nervous system taurine levels, Neurology, 28(4): 331-2, 1978.

Baskin and Finney, The Effects of Taurine on Excitable Tissues (1981),2152 studied the effect of PHT on taurine concentrations in the rat brain. They found that PHT (25 mg/kg), one hour prior to measurement, increased cerebellar, brainstem and cerebral taurine. At 50 mg/kg PHT and above, there was reduction in taurine levels. The authors suggest that PHT exerts its therapeutic effect by increasing endogenous taurine levels.

2152. Baskin, S.I. and Finney, C.M., The Effects of Taurine on Excitable Tissues, 405-18, Spectrum Publications, 1981. 

Pozdeev, Mediator Processes in Epilepsy (1983),2878 studied the effects of PHT on rat brain neurotransmitter systems. Whole brain analysis of rats treated with PHT, 37.5 mg/kg twice a day, intraperitoneally, for seven days, showed increased levels of taurine (48%). Treatment with PHT, 75 mg/kg twice a day for three days, which led to toxicity in some animals, decreased taurine levels (50%). Taurine levels normalized in these animals with continued PHT treatment.

2878. Pozdeev, V. K., The effect of diphenylhydantoin on the function of the brain transmitter systems, Mediator Processes in Epilepsy, Nauka, Leningrad, 85-92, 1983.

Gurevich, Matveeva, Ogurechnikov and Korovkina, Farmakologiia i Toksikologiia (1984),2562 found that PHT increased incorporation of [14C]-taurine by rat cerebral cortex microsomes, suggesting the importance of PHT's effects on intracellular membranes. The greatest effect (doubling of incorporation) was seen at 400 µM PHT. Higher doses were inhibitory. PHT (200 µM) increased [14C]-taurine uptake in cultured C1300 neuroblastoma cells. PHT had no effects on [14C]-glycine incorporation. Phenobarbital had no effects on either taurine or glycine incorporation. The authors suggest that PHT's effects on taurine may be important in its modulation of nervous system hyperexcitability.

2562. Gurevich, V. S., Matveeva, I. M., Ogurechnikov, V. I., Korovkina, G. V., Effect of diphenylhydantoin on taurine binding by subcellular fractions of nerve cells, Farmakol. Toksikol. 47(6): 74-7, 1984.

Izumi, Kishita, Nakagawa, Huxtable, Shimizu, Koja and Fukuda, Progress in Clinical and Biological Research (1985), 2614 reported that treatment of mice with 1% guanidinoethane sulfonate for nine days lowered taurine levels by 24%. Under these circumstances, the effectiveness of PHT and phenobarbital against maximal electroshock seizures was less.

See also Refs. 2513, 2615, 2786, 2851.

2614. Izumi, K., Kishita, C., Nakagawa, K., Huxtable, R. J., Shimizu, T., Koja, T., Fukuda, T., Reduced taurine contents and modification of anticonvulsive effects of phenobarbital and phenytoin by guanidinoethane sultanate in mice, Prog. Clin. Biol. Res., 179: 425-34, 1985.
2513. Frigyesi, T. L., Lombardini, J. B., Augmentation of thalamo-motor cortico-cerebellar epileptogenesis by taurine and its antagonism by diphenlyhydantoin, Life Sci., 24: 1251-60,1979.
2615. Izumi, K., Kishita, C., Nakagawa, K., Huxtable, R. J., Shimizu, T., Koja, T., Fukuda, T., Modification of the antiepileptic actions of phenobarbital and phenytoin by the taurine transport inhibitor, guanidinoethane sultonate, Eur. J. Pharmacol., 110: 219-24, 1985.
2786. Meldrum, B. S., Anlezark, G. M., Ashton, C. G., Horton, R. W., Sawaya, C. B., Neurotransmitters and anticonvulsant drug action, Post-Traumatic Epilepsy and Pharmacological Prophylaxis, Majokowski, J., Ed., Polish Chapter of the Int. League Against Epilepsy, 139-53, 1977.
2851. Patsalos, P. N., Lascelles, P. T., Changes in regional brain levels of amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenylhydantoin, phenobarbitone, sodium valproate, ethosuximide, and sulthiame in the rat, J. Neurochem., 36(2): 688-95, 1981.