Studies in Humans

These studies deal with normal human beings. For more detailed summaries, see Clinical: Thought, Mood and Behavior section.

Haward, Drugs and Cerebral Function (1970),1139 found PHT (150 mg) effective to a significant degree in improving concentration in twelve college students.

1139. Haward, L. R. C., Effects of sodium diphenylhydantoinate and pemoline upon concentration: a comparative study, Drugs and Cerebral Function, 103-120, Smith, W. L., Ed., Charles C Thomas, 1970.

Smith and Lowrey, Drugs, Development and Cerebral Function (1972),1564 in a double-blind study, found that PHT (100 mg, t.i.d.) improved cognitive performance to a significant level in twenty volunteer hospital employees.

1564. Smith, W. L. and Lowrey, J. B., The effects of diphenylhydantoin on cognitive functions in man, Drugs, Development, and Cerebral Function, Smith, W. L., Ed., Charles C Thomas, 344-351, 1972.

Haward, Revue de Medecine Aeronautique et Spatiale (1973),1140 found PHT (150 mg) significantly improved performance in three separate groups of pilots in simulated flying and radar-fixing tasks.

1140. Haward, L. R. C., Effects of DPH (sodium diphenylhydantoinate) upon concentration in pilots, Rev. Med. Aeronautique Spatiale, 12: 372-374, 1973.

Houghton, Latham and Richens, European Journal of Clinical Pharmacology (1973),1168 examined the effect of PHT in six normal volunteers with regard to critical flicker fusion threshold (CFF). No significant change in CFF was observed at 200, 300 and 400 mg of PHT, as tested hourly from one to seven hours after ingestion of PHT.

1168. Houghton, G. W., Latham, A. N., and Richens, A., Difference in the central actions of phenytoin and phenobarbitone in man, measured by critical flicker fusion threshold, Europ. J. Clin. Pharmacol., 6: 57-60, 1973.

Smith and Lowrey, Journal of the American Geriatrics Society (1975),1565 in a double-blind study, found improvement in cognitive functions in a group of elderly normal subjects given PHT, 100 mg, twice daily.

1565. Smith, W. L. and Lowrey, J. B., Effects of diphenylhydantoin on mental abilities in the elderly, J. Amer. Geriat. Soc., 23: 207-211, 1975.

Barratt, Faulk, Brandt and Bryant, Neuropsychobiology (1986),2311 used brain mapping techniques to examine the effects of PHT on the N100 sensory visual potential, as well as the late positive complex (LPC), which reflects cognitive processing. The authors emphasize that augmentation of the N100 potential is associated with impulsivity and attentional distraction.The N100 and LPC potentials were recorded from six normal subjects given the task of counting a series of bright and dim light flashes. Recordings were made before, and one hour after, the subject received either PHT (100 mg) or placebo, depending on the trial. PHT significantly reduced the intensity response of N100 at the vertex and anterior temporal sites, with a lesser reduction at the frontal pole.* In addition, PHT enhanced the frontal negative portion of the slow wave LPC component, but not the positive portion of the slow wave or P300 LPC components. The authors comment that their findings are consistent with behavioral evidence that PHT reduces impulsivity and improves concentration.

* Plasma levels of PHT at one hour ranged from 0.6 to 0.8 g/ml, indicating that plasma levels do not always correlate with PHT's effects.

2311. Barratt, E. S., Faulk, D. M., Brandt, M. E., Bryant, S. C., Effects of phenytoin on N100 augmenting/reducing and the late positive complex of the event-related potential: a topographic analysis, Neuropsychobiology, 15: 201-7, 1986.