DESIGN OF COMPOUNDS WITH ANTICONVULSANT ACTIVITY AMONG NMDA-RECEPTOR LIGANDS
- Authors: Brusina MA1, Kubarskaya LG1, Iljin VV1, Nikolaev DN1, Piotrovskiy LB1
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Affiliations:
- Institute of Experimental Medicine, Saint Petersburg
- Issue: Vol 19, No 1S (2019)
- Pages: 225-226
- Section: Articles
- Published: 15.12.2019
- URL: https://journals.eco-vector.com/MAJ/article/view/19409
- ID: 19409
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Abstract
NMDA receptors play an important role in the development of immune responses. Therefore, the design of NMDAergic compounds presents great interest in various areas, including immunology. We have previously shown that some imidazole-4,5-dicarboxylic acid (IDA) derivatives are ligands of these receptors, and can exhibit both agonistic and antagonistic activities. In continuation of these studies and in attempt to establish the main structural parameters that determine the type of the activity, we developed a general method for synthesis of 1-, 2-mono and 1,2-disubstituted IDA derivatives. To establish the structure-activity relationship in the series under investigation, which include about 30 compounds, we try to find correlations of biological activity with the structure of compounds and some their physicochemical parameters (for example, partition coefficients between the lipophilic and hydrophilic phases). Pharmacological analysis in vivo of this set in various models under ip administration showed that a part of them induces a pre-convulsive state in mice of the CBA line, while the other part has a pronounced anticonvulsant effect on the NMDA-induced seizures. Thus, in the series of compounds under investigation substances that are both convulsants and anticonvulsants were found. The results of this study will allow us to design new drugs with anticonvulsant action.
Full Text
NMDA receptors play an important role in the development of immune responses. Therefore, the design of NMDAergic compounds presents great interest in various areas, including immunology. We have previously shown that some imidazole-4,5-dicarboxylic acid (IDA) derivatives are ligands of these receptors, and can exhibit both agonistic and antagonistic activities. In continuation of these studies and in attempt to establish the main structural parameters that determine the type of the activity, we developed a general method for synthesis of 1-, 2-mono and 1,2-disubstituted IDA derivatives. To establish the structure-activity relationship in the series under investigation, which include about 30 compounds, we try to find correlations of biological activity with the structure of compounds and some their physicochemical parameters (for example, partition coefficients between the lipophilic and hydrophilic phases). Pharmacological analysis in vivo of this set in various models under ip administration showed that a part of them induces a pre-convulsive state in mice of the CBA line, while the other part has a pronounced anticonvulsant effect on the NMDA-induced seizures. Thus, in the series of compounds under investigation substances that are both convulsants and anticonvulsants were found. The results of this study will allow us to design new drugs with anticonvulsant action. Keywords: NMDA receptors; structure-activity relationships; seizures; antiseizure activity.×
About the authors
M A Brusina
Institute of Experimental Medicine, Saint Petersburg
L G Kubarskaya
Institute of Experimental Medicine, Saint Petersburg
V V Iljin
Institute of Experimental Medicine, Saint Petersburg
D N Nikolaev
Institute of Experimental Medicine, Saint Petersburg
L B Piotrovskiy
Institute of Experimental Medicine, Saint Petersburg