Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity

Neuroreport. 2001 Jul 20;12(10):2255-8. doi: 10.1097/00001756-200107200-00042.

Abstract

Lamotrigine (LAG) is an antiepileptic drug which is believed to suppress seizures by inhibiting the release of excitatory neurotransmitters. The present study was aimed at investigating the effect of LAG on the 4-aminopyridine (4AP)-evoked glutamate release in cerebrocortical nerve terminals (synaptosomes). LAG inhibited the release of glutamate evoked by 4AP in a concentration-dependent manner. This inhibitory effect was associated with a reduction in the depolarization-evoked increase in the cytoplasmic free Ca2+ concentration ([Ca2+]C). In addition, LAG did not alter the resting synaptosomal membrane potential or 4AP-evoked depolarization. Furthermore, ionomycin-evoked glutamate release was not affected by LAG. Based on these results, we suggest that presynaptic calcium influx blockade and inhibition of glutamate release may underlie the mechanism of action of LAG. These action may also contribute to their neuroprotective properties in excitotoxic injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glutamic Acid / metabolism*
  • Lamotrigine
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Synaptosomes / drug effects*
  • Synaptosomes / metabolism
  • Triazines / pharmacology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Excitatory Amino Acid Antagonists
  • Triazines
  • Glutamic Acid
  • 4-Aminopyridine
  • Lamotrigine