Glutamatergic antagonism: Effects on lidocaine-induced seizures in the rat

C. McFarlane, D. S. Warner, F. Dexter, M. M. Todd

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16 Scopus citations


We tested the hypothesis that glutamate receptor antagonists increase the dose of lidocaine required to induce seizure activity. Sprague-Dawley rats were anesthetized with halothane in 40% O2/balance N2 and mechanically ventilated. After surgical preparation, halothane was discontinued. Normocapnia, normoxia, and normothermia were maintained. The electroencephalogram (EEG) and arterial blood pressure were monitored continuously. Rats were then randomized to one of six groups (control, one of three intravenous [IV] bolus doses of the competitive glutamate N-methyl-D- aspartate [NMDA] receptor antagonist CGS 19755, or one of two IV bolus and continuous infusion regimens of the competitive glutamate α-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist 2,3-dihydroxy- 6-nitro-7-sulfamoyl-benzo(F)quinoxalline [NBQX]). Thirty minutes after onset of CGS 19755 or NBQX administration (end-tidal halothane <0.2%), rats received a continuous IV infusion of 1.5% lidocaine until EEG seizures occurred. The duration of the infusion (min) and total lidocaine dose (mg/kg) administered were recorded. CGS 19755 increased the lidocaine seizure threshold in a log-linear dose-dependent fashion (P < 10-6). The largest dose of CGS 19755 (112.5 mg/kg) increased the time to initial EEG seizure activity more than twofold (e.g., control = 12.6 ± 2.6 min; CGS 19755 = 28.6 ± 6.9 min). The effect of AMPA receptor antagonism was less obvious because treatment resulted in an EEG morphology dissimilar to that observed in the CGS 19755 or control groups. Our findings indicate that competitive NMDA receptor antagonists (e.g., CGS 19755) increase the dose of lidocaine required for seizures. Given the known NMDA receptor specificity of CGS 19755, the data demonstrate that lidocaine-induced seizure activity can be modulated by antagonism of glutamatergic receptors.

Original languageEnglish (US)
Pages (from-to)701-705
Number of pages5
JournalAnesthesia and analgesia
Issue number4
StatePublished - 1994


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