Bupivacaine-induced convulsion is suppressed by MK-801

Not only the facilitation of inhibitory synapses but also the suppression of excitatory synapses may be effective in treating convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and hemodynamic changes were studied.

Cortex and hippocampal (A4; L5.5; H8) electroencephalogram (EEG), heart rate, and mean arterial pressure were measured in 21 cats anesthetized with urethane. Blood samples were obtained when cats demonstrated arrhythmias, convulsed, and became hypotensive. In the control group (n = 7), bupivacaine was continuously infused until a hypotensive state of 40 mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously 15 minutes before the bupivacaine injection. In the MK-801 treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the appearance of convulsive EEG after the bupivacaine injection.

Bupivacaine produced convulsion in the control group (17.1 +/- 2.4 microg/mL), but not in the MK-801 pretreated group. In the treatment group, convulsive EEG was suppressed gradually after injection of MK-801. The mean plasma bupivacaine concentrations (microg/mL) reaching arrhythmia and hypotension were 9.5 +/- 2.9 and 23.0 +/- 3.0, respectively, in the control group; 10.9 +/- 3.5 and 22.5 +/- 4.9, respectively, in the MK-801 pretreated group; and 7.5 +/- 1.6 and 21.0 +/- 3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and heart rate did not differ among the three groups.

These results demonstrated that one mechanism of bupivacaine-induced convulsion is the excitatory neurotransmitter system in central nervous system and that MK-801 is effective in suppressing the convulsion without any effects on hemodynamics.