Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV

Eur J Pharmacol. 1998 Sep 4;356(2-3):149-57. doi: 10.1016/s0014-2999(98)00526-3.


Electrophysiological studies were carried out on the presynaptic inhibitory action of the group II metabotropic glutamate (mGlu) receptor agonists (+)-2-aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) and (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in three paths of the rat hippocampus, the medial and lateral perforant path to the dentate gyrus, and the Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent reversible inhibition of the field excitatory postsynaptic potential (EPSP) in the medial and lateral perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/- 58 nM, respectively. Maximal inhibition by LY354740 was much greater in the medial path (about 80%) than in the lateral path (about 50%). No inhibition was observed in CA1. A presynaptic inhibition was confirmed by LY354740 inducing dose-dependent changes in paired-pulse depression/facilitation. DCG-IV had a similar action to LY354740, but with a lower potency.

Publication types

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

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / pharmacology*
  • Cyclopropanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Presynaptic Terminals / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Synaptic Transmission / drug effects*


  • Bridged Bicyclo Compounds
  • Cyclopropanes
  • Excitatory Amino Acid Agonists
  • Receptors, Metabotropic Glutamate
  • 2-(2,3-dicarboxycyclopropyl)glycine
  • eglumetad
  • Glycine