Disease relevance of LY341495

• LY341495 reduced glioma cell proliferation at concentrations lower than 100 nm, which are considered as selective for mGlu2/3 receptors [1].
• The preferential mGlu2/3 receptor antagonist, LY341495, reduces the frequency of spike-wave discharges in the WAG/Rij rat model of absence epilepsy [2].
• This inhibition of hyperprolactinemia could be prevented by pretreatment with LY341495, a Group II mGlu receptor antagonist [3].
• Treatment of the goldfish with the brain permeant mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.) amplified anoxic damage throughout the brain and enabled the induction of cell death by anoxia in the telencephalon [4].
• Infusion of LY341495 (10 mg/kg per day) also reduced the growth of brain tumors, as assessed by magnetic resonance imaging analysis carried out every seven days [5].

Psychiatry related information on LY341495

• Additionally, LY341495 alone increased PCP-induced motor activity and head movements suggesting that normal levels of NAAG act to moderate the effect of PCP on motor activation via a group II mGluR [6].
• LY341495 alone increased waking by reducing NREM and REM sleep [7].
• High doses of AVP4-9 exacerbated the PA task performance impairment induced by LY341495 (an mGluR2/3 antagonist), and PMA injection (1 mug) also exacerbated the impairment induced by the antagonist [8].

High impact information on LY341495

• The mGluR3 and group II antagonists beta-NAAG and LY341495 blocked these actions [9].
• The anti-allodynic effect induced by APDC was inhibited by pretreatment with LY341495, a group II mGluR antagonist [10].
• Down-regulation of beta-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive [11].
• Group II selective mGluR receptor blockade with LY341495 (1-10 microm) did not alter the rats' behaviour or hippocampal amino acid levels [12].
• To test the hypothesis that this effect of ZJ43 was mediated by increasing the activation of mGluR3 via increased levels of extracellular NAAG, the group II mGluR selective antagonist LY341495 was co-administered with ZJ43 prior to PCP treatment [6].

Chemical compound and disease context of LY341495

• Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice [13].

Biological context of LY341495

• In two selected cultures (MZC-12 and FCN-9), the mGlu2/3 receptor antagonist, LY341495, slowed cell proliferation when applied to the growth medium from the second day after plating [1].
• 3. The depression of the CT EPSP caused by L-AP4 was reversed using the group III antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 1 mM), and the group II/III antagonist LY341495 (3 microM), but not using the group II antagonist (2S)-alpha-ethylglutamic acid (300 microM) [14].
• The anti-proliferative effect of LY341495 was confirmed by measuring [methyl-3H]-thymidine incorporation in cultures arrested in G0 phase of the cell cycle and then stimulated to proliferate by the addition of 10% fetal calf serum or 100 ng/mL of epidermal growth factor (EGF) [1].
• In rat hippocampal slices, LY341495 eliminated 30 microM DHPG-stimulated PI hydrolysis and 100 microM (1S,3R)-ACPD-inhibition of forskolin-stimulated cAMP formation at concentrations of 100 and 0.03 microM, respectively [15].
• Among the human group III mGlu receptors, the most potent inhibition of L-2-amino-4-phosphonobutyric acid (L-AP4) responses was seen for LY341495 at mGlu8, with an IC50 of 0.17 microM [16].

Anatomical context of LY341495

• 4. Neither MAP4 nor LY341495 had any effect on the CT EPSPs evoked by 10 Hz trains of five stimuli, indicating the lack of endogenous activation of group III mGlu receptors in the thalamus during short bursts of cortical input [14].
• In contrast to LY341495, changes in c-Fos expression following LY354740 were more modest and not generally widespread (decreased in 1 region, dentate gyrus; and increased in 13 out of 52 regions) [17].
• Although the rank order of potency of LY341495 was the same on native rat and cloned human mGlu receptors, there was a compression in the selectivity between group II and III mGlu receptors, expressed in the spinal cord [18].
• The selective mGlu2/3 receptor antagonist LY341495 exacerbates behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons [19].
• Field EPSPs evoked by optic tract stimulation under conditions of GABA receptor blockade were reduced by DCPG by up to 67.8+/-5.46% (EC(50) 1.25+/-0.56 microM), and this effect could be antagonised by LY341495 at a concentration (300 nM) known to be effective at mGlu8 receptors but not at mGlu4 or mGlu7 receptors [20].

Associations of LY341495 with other chemical compounds

• Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495) [21].
• The application of group II mGluR antagonist (LY341495) alone delayed the recovery of PGE2- and carrageenan-induced mechanical allodynia [22].
• Activation of presynaptic group II mGlu autoreceptors by synaptically released glutamate, as revealed by a LY341495-mediated increase in the relative amplitude of a test fEPSP evoked after a conditioning burst, was observed in both the dentate gyrus and the stratum lacunosum of wild-type, but not mGlu2 -/- mice [23].
• In contrast, LY341495 did not block the phosphoinositide hydrolysis response to MHI in rat cortical slices [24].
• In addition, 1S,3R-ACPD-stimulated PI hydrolysis was no longer enhanced in imipramine-treated rats when the mGlu2/3 component of the PI response was abrogated by the antagonist, LY341495 [25].

Gene context of LY341495

• In functional assays, we previously described LY341495 as a highly potent and selective mGlu2 and mGlu3 receptor antagonist [26].
• LY341495 was less potent at mGlu7 (IC50 = 0.99 microM) and least potent at mGlu4 (IC50 = 22 microM) [16].
• LTP proved insensitive to the selective mGluR2/3 antagonists (2S)-alpha-ethylglutamic acid and LY341495, either spinally or intravenously delivered [27].
• Finally, we found that the novel mGluR antagonist LY341495 completely blocked the activation of mGluR1 and mGluR5 and blocked the phosphoinositide hydrolysis response to DHPG in rat cortical slices [24].
• LY341495 competitively antagonised DHPG-stimulated PI hydrolysis in AV12-664 cells expressing either human mGlu1 or mGlu5 receptors with Ki-values of 7.0 and 7.6 microM, respectively [15].

Analytical, diagnostic and therapeutic context of LY341495

• LY341495 also depressed low-frequency and stimulated high-frequency EEG power [7].
• Pretreatment with LY379268 reduced cocaine self-administration and cocaine-induced reinstatement of drug seeking in a dose-dependent, LY341495-reversible manner [28].
• Rats with implanted electrodes were injected with 1, 5, or 10 mg/kg LY341495 at hour 5.5 of the dark period [7].
• MGS0039 (0.3-3 mg/kg, i.p.) as well as LY341495 (0.1-3 mg/kg, i.p.) had dose-dependent antidepressant-like effects in the rat forced swim test and in the mouse tail suspension test [29].
• This hyperlocomotor response was absent in rats tested with a combination of LY341495 and the group II mGluR agonist LY379268 (1.0mg/kg, i.p.). In a second experiment, different rats were tested following microinjections into the NAcc (saline or LY341495, 0.1, 10 or 100mug/0.5mul/side) [30].

References