Effects of metabotropic glutamate receptor antagonists on a rat model of maximum electroshock

2021 ◽  
Vol 29 (2) ◽  
pp. 193-200
Author(s):  
Valentina G. Bashkatova ◽  
Sergey K. Sudakov
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Thiobarbituric Acid ◽  
Secondary Products ◽  
Receptor Antagonists ◽  
Metabotropic Receptor ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Male Wistar Rats ◽  
Convulsive Seizures ◽  
The Brain

AIM: This study aimed to investigate the effect of metabotropic glutamate (mGlu) receptor antagonists on the development of seizure caused by maximum electric shock (MES) and the content of lipid peroxidation (LPO) products in the brain of rats. MATERIALS AND METHODS: Experiments were carried out on male Wistar rats (n = 87) with a mass of 180210 g. In this work, MES was administered. Selective antagonists of I and V subtype mGlu receptors were administered 1 h before MES was administered. Control rats were injected an equivalent amount of saline. The intensity of LPO processes was assessed in terms of the level of secondary products reacting with thiobarbituric acid via a spectrophotometric method. RESULTS: MES led to the development of pronounced clonictonic seizures and increased the level of LPO products in the cerebral cortex of rats by more than threefold. A selective antagonist of subtype V mGlu receptors almost completely stopped the tonic phase of rat seizures and largely prevented the intensification of LPO processes caused by MES. Tonic convulsions were observed in 44% of the experimental animals after the administration of a selective subtype I mGlu receptor antagonist. This antagonist also partially reduced the content of LPO products caused by the effect of MES. CONCLUSION: Thus, mGlu receptors are involved in the development of MES-induced seizures in rats. The most pronounced weakening of convulsive manifestations and the prevention of an increase in the level of LPO products caused by MES were observed in the block of subtype V mGlu receptors. The obtained data confirmed the possibility of using subtype V metabotropic receptor antagonists as anticonvulsants for the treatment of epilepsy with generalized convulsive seizures.

Synthesis of heterocyclic enol ethers and their use as group 2 metabotropic glutamate receptor antagonists

1999 ◽  
Vol 9 (15) ◽  
pp. 2173-2176 ◽  
Author(s):  
Sabine Kolczewski ◽  
Geo Adam ◽  
Heinz Stadler ◽  
Vincent Mutel ◽  
Jürgen Wichmann ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Antagonists ◽  
Enol Ethers ◽  
Metabotropic Glutamate ◽  
Glutamate Receptor Antagonists ◽  
Group 2

Properties of a presynaptic metabotropic glutamate receptor in rat neostriatal slices

1993 ◽  
Vol 69 (4) ◽  
pp. 1236-1244 ◽  
Author(s):  
D. M. Lovinger ◽  
E. Tyler ◽  
S. Fidler ◽  
A. Merritt
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Field Potential ◽  
Population Spike ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Metabotropic Receptor ◽  
Whole Cell ◽  
Metabotropic Glutamate ◽  
Cell Recording

1. The effect of the metabotropic glutamate receptor agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) on glutamatergic transmission at corticostriate synapses was examined using slices of neostriatum. Field potential recordings were performed in slices from adult animals, and the effects of t-ACPD on the synaptically driven population spike were examined. Tight-seal whole-cell recordings were made in slices from 2 to 4-wk-old rats, and effects of t-ACPD on the amplitude of excitatory postsynaptic potentials (EPSPs) and postsynaptic neuronal membrane properties were examined. In addition, the effects of putative metabotropic receptor agonists and antagonists and 4-aminopyridine were examined. The ability of these compounds to mimic t-ACPD or block its actions were determined. 2. Application of t-ACPD (5-100 microM) depressed the maximal amplitude of the synaptically driven population spike during field potential recording. This compound likewise depressed the amplitude of EPSPs observed with whole-cell recording. The 1S,3R isomer of t-ACPD was effective in depressing transmission, whereas the 1R,3S isomer was without effect at 50 microM. The cis isomer of ACPD (c-ACPD) also depressed transmission at concentrations from 25 to 100 microM. 3. Depression of population spike or EPSP amplitude by t-ACPD was not altered in the presence of the putative metabotropic receptor antagonist L-aminophosphonopropionic acid (AP3, 1 mM). In addition, the depressant action of t-ACPD on the population spike was not mimicked by aminophosphonobutyric acid, which has been shown to produce synaptic depression at other excitatory synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Predicting Compound Selectivity by Self-Organizing Maps: Cross-Activities of Metabotropic Glutamate Receptor Antagonists

ChemMedChem ◽  
2006 ◽  
Vol 1 (10) ◽  
pp. 1066-1068 ◽  
Author(s):  
Tobias Noeske ◽  
Britta C. Sasse ◽  
Holger Stark ◽  
Christopher G. Parsons ◽  
Tanja Weil ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Antagonists ◽  
Self Organizing Maps ◽  
Metabotropic Glutamate ◽  
Glutamate Receptor Antagonists ◽  
Self Organizing

scholarly journals Design, Synthesis and Characterization of a New Series of Fluorescent Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulators

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1532
Author(s):  
Víctor Fernández-Dueñas ◽  
Mingcheng Qian ◽  
Josep Argerich ◽  
Carolina Amaral ◽  
Martijn D.P. Risseeuw ◽  
...  
Keyword(s):  
Binding Sites ◽  
Metabotropic Glutamate Receptor ◽  
Allosteric Modulators ◽  
Design Synthesis ◽  
Metabotropic Glutamate ◽  
Animal Disease Models ◽  
Fluorescent Ligands ◽  
The Brain

In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter’ systems, thus providing safe and effective treatments for a number of central nervous system diseases. The metabotropic glutamate type 5 receptor (mGlu5R) has been shown to possess a druggable allosteric binding domain. Accordingly, novel allosteric ligands are being explored in order to finely regulate glutamate neurotransmission, especially in the brain. However, before testing the activity of these new ligands in the clinic or even in animal disease models, it is common to characterize their ability to bind mGlu5Rs in vitro. Here, we have developed a new series of fluorescent ligands that, when used in a new NanoBRET-based binding assay, will facilitate screening for novel mGlu5R allosteric modulators.

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