Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord.
Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000201:enzymology*; D003580:Cytochromes / Q000378:metabolism; D003864:Depression, Chemical; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D010406:Penicillins; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013116:Spinal Cord / Q000201:enzymology*
D003580:Cytochromes; D010406:Penicillins; D009243:NAD; D010672:Phenytoin; D011188:Potassium