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

Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were administered 50% MgSO4 or 0.9% NaCl intravenously (IV) (20 microL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCl, 0.8% MgSO4, or 2.0% MgSO4 (10 microL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg2+] was greater in the MgSO4 group (5.1 +/- 1.5 mg/dL vs 1.8 +/- 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO4 = 19 +/- 2 mg/kg; saline = 23 +/- 5 mg/kg) nor brain [Mg2+] (MgSO4 = 794 +/- 17 micrograms/g; saline = 788 +/- 33 micrograms/g) were changed. In Experiment 2, intracerebroventricular MgSO4 increased both brain [Mg2+] (2% MgSO4 = 923 +/- 79 micrograms/g; saline = 788 +/- 35 micrograms/g) and the lidocaine seizure dose (2% MgSO4 = 39 +/- 7 mg/kg; saline = 26 +/- 3 mg/kg). Although intracerebroventricular administration of MgSO4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg2+] and therefore offers no protection from lidocaine-induced seizures in this model.