LY354740

LY354740 is an agonist of the group II metabotropic glutamate receptor (mGluR) subtypes mGluR2 and mGluR3 (K_is = 99 and 94 nM, respectively).¹ It inhibits forskolin-stimulated cAMP accumulation in cells expressing human mGluR2 and mGluR3 (EC₅₀s = 5.1 and 24.3 nM, respectively) and is selective for mGluR2 and mGluR3 over mGluR4, mGluR7, mGluR1a, and mGluR5a (EC₅₀s = >100 µM).^2,3 LY354740 suppresses electrically stimulated excitatory postsynaptic potentials (EPSPs) in rat striatal neurons (EC₅₀ = 20 nM) and excitatory postsynaptic currents (EPSCs) induced by serotonin (Item No. 14332) in rat medial prefrontal cortex in vitro (EC₅₀ = 89.1 nM).^1,4 LY354740 (5 mM) iontophoretically ejected into the ventrobasal thalamus of rats reduces sensory inhibition by 20% compared to control in an alternating test, condition-test paradigm.⁵ It attenuates the effects of PCP on working memory, stereotypy, locomotion, and cortical glutamate efflux in a rat model of schizophrenia when administered at a dose of 10 mg/kg.⁶ LY354740 also shows efficacy in animal models of anxiety, epilepsy, and withdrawal from nicotine and morphine.^1,7

WARNING This product is not for human or veterinary use.

1. Rorick-Kehn, L.M., Johnson, B.G., Burkey, J.L., et al. Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (−)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039). J. Pharmacol. Exp. Ther. 321(1), 308-317 (2007).

2. Schoepp, D.D., Johnson, B.G., Wright, R.A., et al. LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Neuropharmacology 36(1), 1-11 (1997).

3. Monn, J.A., Valli, M.J., Massey, S.M., et al. Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): Identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J. Med. Chem. 42(6), 1027-1040 (1999).

4. Marek, G.J., Wright, R.A., Schoepp, D.D., et al. Physiological antagonism between 5-hydroxytryptamine2A and group II metabotropic glutamate receptors in prefrontal cortex. J. Pharmacol. Exp. Ther. 292(1), 76-87 (2000).

5. Copeland, C.S., Neale, S.A., and Salt, T.E. Actions of xanthurenic acid, a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus. Neuropharmacology 66, 133-142 (2013).

6. Moghaddam, B., and Adams, B.W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281(5381), 1349-1352 (1998).

7. Schoepp, D.D., Jane, D.E., and Monn, J.A. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38(10), 1431-1476 (1999).