Comparison of the antiepileptic properties of transmeningeally delivered muscimol, lidocaine, midazolam, pentobarbital and GABA, in rats

Neurosci Lett. 2010 Jan 29;469(3):421-4. doi: 10.1016/j.neulet.2009.12.042. Epub 2009 Dec 23.


This study compared the potencies of epidurally delivered muscimol, lidocaine, midazolam, pentobarbital and gamma-aminobutyric acid (GABA) to prevent focal neocortical seizures induced by locally applied acetylcholine (Ach), in rats (n=5). An epidural cup was chronically implanted over the right somatosensory cortex in each animal, with epidural EEG electrodes placed posterior to the edge of the cup. After recovery, either artificial cerebrospinal fluid (ACSF; control solution) or one of the five drugs was delivered into epidural cup, followed by Ach administration into the cup to induce seizures. EEG seizure duration ratio was calculated for each drug delivery/seizure induction session to determine the potency of ACSF and the drugs to prevent the focal Ach-seizures. The concentration of all examined drug solutions was 1.0mM. ACSF, lidocaine, midazolam, pentobarbital and GABA all failed to prevent the Ach-induced neocortical EEG seizures, yielding EEG seizure duration ratios ranging from 0.41 to 0.80. In contrast, muscimol pretreatment fully prevented the development of ictal EEG in all animals. These results suggest that when used at low concentration muscimol was the best of the five drugs for transmeningeal pharmacotherapy trials for focal neocortical epilepsy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Electrodes, Implanted
  • Electroencephalography
  • Lidocaine / administration & dosage
  • Lidocaine / pharmacology
  • Midazolam / administration & dosage
  • Midazolam / pharmacology
  • Muscimol / administration & dosage
  • Muscimol / pharmacology
  • Pentobarbital / administration & dosage
  • Pentobarbital / pharmacology
  • Rats
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / physiopathology*
  • Somatosensory Cortex / drug effects*
  • Somatosensory Cortex / physiopathology*
  • Time Factors
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / pharmacology


  • Anticonvulsants
  • Muscimol
  • gamma-Aminobutyric Acid
  • Lidocaine
  • Pentobarbital
  • Acetylcholine
  • Midazolam