Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat. The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures. 