The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat.

Lidocaine and MgSO 4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO 4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgS 4 administration is as effective as intracerebroventricular MgSO 4 infusion. In Experiment 1, rats were administered 50% MgSO 4 or 0.9% NaCl intravenously (IV) (20 μL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCI, 0.8% MgSO 4 , or 2.0% MgSO 4 (10 μL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg 2+ ] was greater in the MgSO 4 group (5.1 ± 1.5 mg/dL vs 1.8 ± 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO 4 = 19 ± 2 mg/kg ; saline = 23 ± 5 mg/kg) nor brain [Mg 2+ ] (MgSO 4 = 794 ± 17 μg/g ; saline = 788 ± 33 μg/g) were changed. In Experiment 2, intracerebroventricular MgSO 4 increased both brain [Mg 2+ ] (2% MgSO 4 = 923 ± 79 μg/g ; saline = 788 ± 35 μg/g) and the lidocaine seizure dose (2% MgSO 4 = 39 ± 7 mg/kg ; saline = 26 ± 3 mg/kg). Although intracerebroventricular administration of MgSO 4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg 2+ ] and therefore offers no protection from lidocaine-induced seizures in this model.