Ly341495

Manufactured by Bio-Techne

Sourced in United Kingdom, United States

LY341495 is a potent and selective non-competitive metabotropic glutamate receptor 2/3 (mGlu2/3) antagonist. It inhibits the activity of mGlu2 and mGlu3 receptors.

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Lab products found in correlation

Ly379268, by Bio-Techne (10 mentions) Dcg 4, by Bio-Techne (7 mentions) Snap lumi4 tb, by PerkinElmer (4 mentions) Dl tboa, by Bio-Techne (3 mentions) Ly354740, by Bio-Techne (3 mentions) Snap green, by PerkinElmer (3 mentions) Formalin, by Xilong (3 mentions) 35s gtpγs, by PerkinElmer (2 mentions) Mk801, by Fujifilm (2 mentions) S 4 carboxyphenylglycine cpg, by Bio-Techne (2 mentions) Ly395756, by Bio-Techne (2 mentions) Picrotoxin, by Bio-Techne (2 mentions) Mk 801, by Merck Group (2 mentions) D ap5, by Bio-Techne (2 mentions) R cpp, by Bio-Techne (2 mentions) Fluvoxamine, by Merck Group (2 mentions) D15 peptide pppqvpsrpnrappg, by Bio-Synthesis (2 mentions) Tetrodotoxin, by Abcam (2 mentions) Ly379268, by Abcam (2 mentions) Snap red, by PerkinElmer (2 mentions)

Close spelling variants of this product

LY341495 disodium salt (4 citations)

51 protocols using ly341495

Pharmacological Manipulation of mGluRs

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For light response recordings, 50–100 nM LY341495 (Tocris) was added to Ames’ media after baseline experiments. At these concentrations, LY341495 is selective for Group II mGluRs (Kingston et al., 1998 (link)). Notably, mGluR3 has not been found in the mammalian retina (Brandstätter et al., 1998 (link)). For paired recordings and SAC pharmacology studies, the aCSF was perfused with 500nM-1μM LY354740 (Tocris), a highly selective Group II mGluR agonist (Schoepp et al., 1997 (link)) after whole-cell recording was established, and 3 μM LY341495 was subsequently used to competitively inhibit mGluR2 activity (Kingston et al., 1998 (link)). To block voltage-gated calcium channels, 300 μM CdCl₂ (Sigma) or combinations of 1 μM ω-conotoxin GVIA (Abcam) and 250 nM ω-agatoxin IVA (Alomone) were added to the aCSF.

Koren D., Grove J.C, & Wei W. (2017). Cross-compartmental modulation of dendritic signals for retinal direction selectivity. Neuron, 95(4), 914-927.e4.

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Borneol and Menthol Analgesic Effects

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Medical Borneol was obtained from Shanghai Hongqiao Traditional Chinese Medicine Co., Ltd. (+)‐Borneol (simply called Borneol in this study), (±)‐menthol (simply called menthol in this study), complete Freund's adjuvant, and capsaicin were purchased from Sigma‐Aldrich. Formalin was purchased from Xilong Chemical Co. AMTB, naloxone, and LY341495 were obtained from TOCRIS. Bicuculline was obtained from Tokyo Chemical Industry. Muscimol was obtained from Enzo Life Sciences. ATP disodium salt was obtained from Sangon Biotech. Ionomycin was purchased from Cayman Chemical. Morphine hydrochloride was obtained from Northeast Pharm.

Wang S., Zhang D., Hu J., Jia Q., Xu W., Su D., Song H., Xu Z., Cui J., Zhou M., Yang J, & Xiao J. (2017). A clinical and mechanistic study of topical borneol‐induced analgesia. EMBO Molecular Medicine, 9(6), 802-815.

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Binding Assay for Metabotropic Glutamate Receptors

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LY341495, DCG-IV and LY379268 were from Tocris Bioscience (Minneapolis, MN, USA). 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) was from Research Biochemicals International (Natick, MA, USA). [³⁵S]GTPγS was purchased from Perkin Elmer (Waltham, MA, USA).

Burgos-Aguilar C., Ferris M.J., Sexton L.L., Sun H., Xiao R., Chen R., Childers S.R, & Howlett A.C. (2020). Metabotropic glutamate 2,3 receptor stimulation desensitizes agonist activation of G-protein signaling and alters transcription regulators in mesocorticolimbic brain regions. Synapse (New York, N.Y.), 75(4), e22190.

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Methamphetamine-induced Behavioral Study

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Male C57BL/6J mice (8‐week‐old; 22‐27 g; Nihon SLC, Inc.) were housed in a room with a 12‐hour light/dark cycle. Lights were turned on at 7 am and turned off at 7 pm. All procedures followed the National Institute of Health Guideline for the Care and Use of Laboratory Animals and were approved by the Animal Experiments Committee of the University of Toyama (Permission Number A2015pha‐21 and A2018pha10). Methamphetamine was purchased from Dainippon Sumitomo Pharmaceutical Co. Ltd. and was dissolved in saline (0.1 mg/mL). LY341495 was purchased from Tocris Bioscience. All other reagents were obtained from standard commercial sources.

Haddar M., Uno K., Hamatani K., Muramatsu S, & Nitta A. (2019). Regulatory system of mGluR group II in the nucleus accumbens for methamphetamine‐induced dopamine increase by the medial prefrontal cortex. Neuropsychopharmacology Reports, 39(3), 209-216.

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Pharmacological Modulation of Neuronal Signaling

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NMDAR antagonist, MK801,15 (link) memantine (MEM), cysteine prodrug, N‐acetyl‐l‐cysteine (NAC),16 (link) and the GABA_A receptor agonist, muscimol (MUS)15 (link) were obtained from Wako Chemicals (Osaka, Japan). The II‐mGluR antagonist LY341495,17 (link) the III‐mGluR antagonist (RS)‐α‐cyclopropyl‐4‐phosphonophenyl glycine (CPPG),17 (link) and the Sxc inhibitor (S)‐4‐carboxyphenylglycine (CPG)18 (link) were purchased from Tocris Bioscience (Bristol, UK).
All compounds were prepared on the day of experiments. MK801, MEM, CPPG, CPG, NAC, and MUS were dissolved in modified Ringer's solution (MRS) or artificial cerebrospinal fluid (ACSF). LY341495 was initially dissolved in 10 mmol L⁻¹ dimethyl sulfoxide and was then diluted to 1 mmol L⁻¹ in MRS. The final concentrations of LY341495 and dimethyl sulfoxide were 1 μmol L⁻¹ and 0.1% (vol vol⁻¹), respectively.
MRS contained 145 mmol L⁻¹ Na⁺, 2.7 mmol L⁻¹ K⁺, 1.2 mmol L⁻¹ Ca²⁺, 1.0 mmol L⁻¹ Mg²⁺, and 154.4 mmol L⁻¹ Cl⁻. The pH was adjusted to 7.4 using 2 mmol L⁻¹ phosphate buffer and 1.1 mmol L⁻¹ Tris buffer.19 (link), 20 (link) ACSF contained 130 mmol L⁻¹ NaCl, 5.4 mmol L⁻¹ KCl, 1.8 mmol L⁻¹ CaCl₂, 1 mmol L⁻¹ MgCl₂, and 5.5 mmol L⁻¹ glucose and was buffered to pH 7.3 using 20 mmol L⁻¹ HEPES.

Okada M., Fukuyama K., Kawano Y., Shiroyama T, & Ueda Y. (2019). Memantine protects thalamocortical hyper‐glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc−. Pharmacology Research & Perspectives, 7(1), e00457.

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In Vivo Drug Delivery Protocol

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For in vivo drug delivery, the animals were imaged as described above and then injected intraperitonially with either MPEP (10 mg/kg; Tocris; dissolved in ddH2O), an mGluR5 antagonist, LY341495 (3 mg/kg; Tocris; dissolved in 1.2eq NaOH and diluted in 0.9% NaCl), an mGluR2/3 antagonist, or vehicle (ddH2O or 0.9% NaCl). The animals were imaged immediately after injection (in the case of MPEP and ddH2O) or within 30–60 min after injection (in the case of LY341495 and 0.9% NaCl).

Kellner V., Kersbergen C.J., Li S., Babola T.A., Saher G, & Bergles D.E. (2021). Dual metabotropic glutamate receptor signaling enables coordination of astrocyte and neuron activity in developing sensory domains. Neuron, 109(16), 2545-2555.e7.

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Pharmacological Modulation of Neurochemical Pathways

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Clozapine was purchased from Sigma (St. Louis, MO, USA). The non-competitive NMDA-R antagonist, MK801 [40 (link)], was obtained from Wako Chemicals (Osaka, Japan). The II-mGluR antagonist (LY341495), the III-mGluR antagonist ((RS)-α-cyclopropyl-4-phosphonophenyl glycine (CPPG)) [41 (link)], and the Sxc inhibitor ((S)-4-carboxyphenylglycine (CPG)) [30 (link),42 (link)] were purchased from Tocris Bioscience (Bristol, UK). The hemichannel and gap-junction blocker, carbenoxolone (CBX) [43 (link)], was obtained from Cosmo Bio (Tokyo, Japan).
LY341495 and CBX were initially dissolved in 10 mM with dimethyl sulfoxide, then diluted to 1 mM with modified Ringer’s solution (MRS) or artificial cerebrospinal fluid (ACSF) [28 (link),44 (link)]. CPPG and CPG were dissolved in MRS or ACSF. CLZ and MK801 were dissolved in MRS, ACSF, or Dulbecco’s modified Eagle’s medium containing 10% fetal calf serum (fDMEM) containing less than 0.1% acetic acid.

Fukuyama K., Kato R., Murata M., Shiroyama T, & Okada M. (2019). Clozapine Normalizes a Glutamatergic Transmission Abnormality Induced by an Impaired NMDA Receptor in the Thalamocortical Pathway via the Activation of a Group III Metabotropic Glutamate Receptor. Biomolecules, 9(6), 234.

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Pharmacological Modulation of Neural Signaling

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Picrotoxin and QX-314 were purchased from Sigma. LY379268, LY395756, and LY341495 were purchased from Tocris Bioscience. VU6001192 and VU0469942 were generously provided by the Vanderbilt Center for Neuroscience Drug Discovery (Vanderbilt University, Nashville, TN).

Johnson K.A., Mateo Y, & Lovinger D.M. (2017). Metabotropic glutamate receptor 2 inhibits thalamically-driven glutamate and dopamine release in the dorsal striatum. Neuropharmacology, 117, 114-123.

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Examining Neurotransmitter Modulation in Addiction

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Methamphetamine HCl (Sigma, St Louis, MO) was dissolved in 0.9%
sterile saline. For both systemic and intracranial administrations, oxytocin
(Cell Sciences, Canton, MA) was dissolved in 0.9% sterile saline, and
the mGluR2/3 antagonist LY341495 (Tocris bioscience, Bristol, UK) was first
dissolved in HCl and then saline. All drug doses were derived from previous work
from our laboratory and others. For systemic injections oxytocin was
administered at 1 mg/kg (Cox et al.,
2013, Zhou et al., 2015 ; Leong et al., 2016 (link)) and LY341495 was
injected at 1 mg/kg (Scofield et al.,
2015; Li et al., 2010). For intracranial administration, oxytocin was
infused at a concentration of 0.6nmol/0.25µl/side (Baracz et al., 2012 ; Cox et
al., 2017). LY341495 was infused at a concentration of
1.3nmol/0.25µl/side based on a range of two efficient doses (Kim
et al, 2015; Richard and Berridge, 2011). Micro infusions
were made by inserting a 33-gauge stainless steel injector (Plastics One,
Roanoke, VA) into the guide cannulae. The injector was connected to a
polyethylene tube (PE-20) and fitted to a 1 µl Hamilton syringe
(Hamilton, NV, USA). Each rat received two consecutive microinjections of either
LY341495 or vehicle followed by oxytocin or saline over a 1 min period.
Injectors were left in place an additional minute to allow for diffusion.

Bernheim A., Leong K.C., Berini C, & Reichel C.M. (2017). Antagonism of mGlu2/3 receptors in the nucleus accumbens prevents oxytocin from reducing cued methamphetamine seeking in male and female rats. Pharmacology, biochemistry, and behavior, 161, 13-21.

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Pharmacological Modulation of Synaptic Transmission

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The following (concentrations of) drugs were delivered through the recording aCSF solution: GABA_A receptor antagonist: Picrotoxin, PTX (50 μM), AMPA receptor antagonist NBQX (1, 2,3,4-Tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulf- onamide hydrate; 10 μM), NMDA receptor antagonist DL-AP5 (DL-2-Amino-5-phosphonopentanoic acid; 25 μM), EAAT blocker DL-TBOA (DL-threo-beta-Hydroxyaspartic acid; 50 μM), Group II mGluR antagonist LY341495 were from Tocris Bioscience (United Kingdom). Barium chloride, BaCl₂ (100 μM) and NMDA antagonist MK-801 [(5S,10R)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine; 10 μM] were from Sigma-Aldrich (United States). Both DL-AP5 and MK-801 completely blocks NMDA receptors under these conditions and are considered equivalent.

Srivastava I., Vazquez-Juarez E, & Lindskog M. (2020). Reducing Glutamate Uptake in Rat Hippocampal Slices Enhances Astrocytic Membrane Depolarization While Down-Regulating CA3–CA1 Synaptic Response. Frontiers in Synaptic Neuroscience, 12, 37.

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