Lewin and Bleck, Epilepsia (1981), 2716 reported that, in mice, PHT (100 mg) intraperitoneally, ten minutes prior to convulsive electroshock, markedly reduced the seizure-induced rise in brain inosine and hypoxanthine, two metabolites of adenosine. The rise in adenosine resulting from a series of subconvulsive shocks was also reduced by PHT.

Phillis and Wu, Comparative Biochemistry and Physiology (1982), 2869 showed that PHT inhibited adenosine uptake by rat brain synaptosomes. PHT reduced this up-take by 20% at 1.5 µM and 50% at 200 µM. Phenobarbital and carbamazepine also inhibited adenosine uptake, but weakly. The authors propose that PHT corrects abnormal neuronal hyperexcitability by inhibiting uptake, and increasing extracellular levels, of adenosine.

Bernard, Wilson, Pastor, Brown and Glenn, Pharmacologist (1983), 2324 noting that PHT, as well as carbamazepine and phenobarbital, inhibit the binding of [3H]-phenylisopropyladenosine to rat brain membranes, reported that the adenosine antagonists, theophylline and caffeine, reduced the protective effects of PHT against maximal electroshock seizures in mice. The authors suggest that PHT may achieve some of its effects on neuronal hyperexcitability through adenosine receptors.

2716. Lewin, E., Bleck, V., Electroshock seizures in mice: effect on brain adenosine and its metabolites, Epilepsia, 577-81, 1981.

2869. Phillis, J. W., Wu, P. H., The effect of various centrally active drugs on adenosine uptake by the central nervous system, Comp. Biochem. Physiol., 72c: 179-87, 1982.
2324. Bernard, P., Wilson, D., Paster, G., Brown, W., Glenn, T. M., Possible involvement of adenosine receptors in the electroshock anticonvulsant effects of carbamazepine, diphenylhydantoin, phenobarbital and diazepam, Pharmacologist, 25 (3): 164, 1983.