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Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6...

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Autores principales: Li, Min, Kang, Ruixia, Shi, Jiangong, Liu, Gengtao, Zhang, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3692431/
https://www.ncbi.nlm.nih.gov/pubmed/23825618
http://dx.doi.org/10.1371/journal.pone.0067060
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author Li, Min
Kang, Ruixia
Shi, Jiangong
Liu, Gengtao
Zhang, Jianjun
author_facet Li, Min
Kang, Ruixia
Shi, Jiangong
Liu, Gengtao
Zhang, Jianjun
author_sort Li, Min
collection PubMed
description Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6)-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A(1) and A(2A) receptors. Furthermore, DPCPX, a selective A(1) receptor antagonist, but not SCH58261, a selective A(2A) receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A(1) receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.
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spelling pubmed-36924312013-07-02 Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures Li, Min Kang, Ruixia Shi, Jiangong Liu, Gengtao Zhang, Jianjun PLoS One Research Article Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6)-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A(1) and A(2A) receptors. Furthermore, DPCPX, a selective A(1) receptor antagonist, but not SCH58261, a selective A(2A) receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A(1) receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy. Public Library of Science 2013-06-25 /pmc/articles/PMC3692431/ /pubmed/23825618 http://dx.doi.org/10.1371/journal.pone.0067060 Text en © 2013 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Min
Kang, Ruixia
Shi, Jiangong
Liu, Gengtao
Zhang, Jianjun
Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title_full Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title_fullStr Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title_full_unstemmed Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title_short Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures
title_sort anticonvulsant activity of b2, an adenosine analog, on chemical convulsant-induced seizures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3692431/
https://www.ncbi.nlm.nih.gov/pubmed/23825618
http://dx.doi.org/10.1371/journal.pone.0067060
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