LY354740 is a Potent and Highly Selective Group II Metabotropic Glutamate Receptor Agonist in Cells Expressing Human Glutamate Receptors

Schoepp, Darryle D.; Johnson, Bryan G.; Wright, Rebecca A.; Salhoff, Craig R.; Mayne, N.G.; Wu, Size; Burnett, J. Paul; Belegaje, R; Bleakman, David; Monn, James A.

doi:10.1016/s0028-3908(96)00160-8

Cited by 217 publications

(128 citation statements)

References 29 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…To our knowledge, these are the first in vivo microdialysis data providing direct evidence that group II mGlu receptors can selectively modulate NE release. These results are consistent with one earlier finding by Vandergriff and Rasmussen (1999), showing that LY354740, a selective but less potent mGlu2/ 3 receptor agonist (Schoepp et al, 1997;Monn et al, 1999), can attenuate morphine-withdrawal-induced activation of LC neurons.…”

Section: Discussionsupporting

confidence: 93%

Group II mGlu Receptor Activation Suppresses Norepinephrine Release in the Ventral Hippocampus and Locomotor Responses to Acute Ketamine Challenge

Lorrain

Schaffhauser

Campbell

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

Group II mGlu receptor agonists (eg LY379268 and LY354740) have been shown to reverse many of the behavioral responses to PCP as well as glutamate release elicited by PCP and ketamine. In the present set of experiments, we used in vivo microdialysis to show that, in addition to reversing PCP-and ketamine-evoked glutamate release, group II mGlu receptor stimulation also prevents ketamine-evoked norepinephrine (NE) release. Pretreating animals with the mixed 2/3 metabotropic glutamate (mGlu2/3) receptor agonist LY379268 (0.3-10 mg/kg) dose-dependently inhibited ketamine (25 mg/kg)-evoked NE release in the ventral hippocampus (VHipp). Ketamine hyperactivity was also reduced in a similar dose range. Following our initial observation on NE release, we conducted a series of microinjection experiments to reveal that the inhibitory effects of LY379268 on VHipp NE release may be linked to glutamate transmission within the medial prefrontal cortex. Finally, we were able to mimic the inhibitory effects of LY379268 on ketamine-evoked NE release by using a novel mGlu2 receptor selective positive modulator. (+/À) 2,2,2-Trifluoroethyl [3-(1-methyl-butoxy)-phenyl]-pyridin-3-ylmethyl-sulfonamide (2,2,2-TEMPS, characterized through in vitro GTPgS binding) at a dose of 100 mg/kg significantly reduced the NE response. Together, these results demonstrate a novel means to suppress noradrenergic neurotransmission (ie by activating mGlu2 receptors) and may, therefore, have important implications for neuropsychiatric disorders in which aberrant activation of the noradrenergic system is thought to be involved.

show abstract

Section: Discussionsupporting

confidence: 93%

Group II mGlu Receptor Activation Suppresses Norepinephrine Release in the Ventral Hippocampus and Locomotor Responses to Acute Ketamine Challenge

Lorrain

Schaffhauser

Campbell

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…We find that two group II mGluR selective agonists, DCG-IV and LY354740 (Schoepp et al, 1997), inhibited glutamate-dependent field potentials and EPSCs, and that this effect was blocked by LY341495 at concentrations selective for group II mGluRs. The effect of LY354740 on EPSCs is potent and concentration-dependent, with maximal depression elicited by 100 nM LY354740.…”

Section: Discussionmentioning

confidence: 75%

Group II and III Metabotropic Glutamate Receptors Suppress Excitatory Synaptic Transmission in the Dorsolateral Bed Nucleus of the Stria Terminalis

Grueter

Winder

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Conditions such as anxiety, drug abuse, and post-traumatic stress disorder are thought to reflect alterations in central nervous system stress and reward circuitry. Recent evidence suggests a key component of this circuitry is the bed nucleus of the stria terminalis (BNST). In particular, regulation of glutamatergic transmission in the BNST plays a critical role in animal performance on anxiety tasks. Metabotropic glutamate receptors (mGluRs) have been implicated in stress and drug addiction and are known to regulate glutamatergic transmission in many brain regions. We have utilized both extracellular field potential and whole-cell patch-clamp recording in an in vitro slice preparation of mouse dorsal anterolateral BNST to determine whether G i/o -linked mGluRs modulate excitatory transmission in this region. We find that activation of group II and group III mGluRs in an in vitro slice preparation of the dBNST causes a depression of excitatory transmission. The depression evoked by group II mGluR activation may represent a form of synaptic plasticity as prolonged activation of the receptor produces a long-term depression of glutamatergic transmission. Based on paired-pulse ratio analysis, initiation of depression by group II and group III mGluR subfamilies appears to, at least in part, involve decreased glutamate release. In total, our data suggest a plausible site of action for some of the anxiolytic effects of group II and group III mGluR agonists.

show abstract

“…LY354740, a glutamate analog, is a highly specific, nanomolar-potent agonist at mGlu2/3 receptors (Schoepp et al, 1997(Schoepp et al, , 2003. LY354740 has evidenced activity in a number of rodent stress and anxiety models, including fear-potentiated startle, elevated plus maze, lactate-induced panic, and stress-induced hyperthermia (Walker et al, 2002;Tizzano et al, 2002;Monn et al, 1997;Shekhar and Keim, 2000;Spooren et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Tolerability of an mGlu2/3 Agonist in the Treatment of Generalized Anxiety Disorder

Dunayevich

Erickson

Levine

et al. 2007

Neuropsychopharmacol

171

View full text Add to dashboard Cite

LY354740 is a Potent and Highly Selective Group II Metabotropic Glutamate Receptor Agonist in Cells Expressing Human Glutamate Receptors

Cited by 217 publications

References 29 publications

Group II mGlu Receptor Activation Suppresses Norepinephrine Release in the Ventral Hippocampus and Locomotor Responses to Acute Ketamine Challenge

Group II mGlu Receptor Activation Suppresses Norepinephrine Release in the Ventral Hippocampus and Locomotor Responses to Acute Ketamine Challenge

Group II and III Metabotropic Glutamate Receptors Suppress Excitatory Synaptic Transmission in the Dorsolateral Bed Nucleus of the Stria Terminalis

Efficacy and Tolerability of an mGlu2/3 Agonist in the Treatment of Generalized Anxiety Disorder

Contact Info

Product

Resources

About