NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for nove...

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Main Authors: Rothan, H.A., Amini, E., Faraj, F.L., Golpich, M., Teoh, T.C., Gholami, K., Yusof, R.
Format: Article
Language:English
Published: Nature Publishing Group 2017
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Online Access:http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf
http://eprints.um.edu.my/19038/
http://dx.doi.org/10.1038/srep45540
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spelling my.um.eprints.190382018-08-30T06:04:59Z http://eprints.um.edu.my/19038/ NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy Rothan, H.A. Amini, E. Faraj, F.L. Golpich, M. Teoh, T.C. Gholami, K. Yusof, R. Q Science (General) R Medicine N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants. Nature Publishing Group 2017 Article PeerReviewed application/pdf en http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf Rothan, H.A. and Amini, E. and Faraj, F.L. and Golpich, M. and Teoh, T.C. and Gholami, K. and Yusof, R. (2017) NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy. Scientific Reports, 7 (1). p. 45540. ISSN 2045-2322 http://dx.doi.org/10.1038/srep45540 doi:10.1038/srep45540
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
language English
topic Q Science (General)
R Medicine
spellingShingle Q Science (General)
R Medicine
Rothan, H.A.
Amini, E.
Faraj, F.L.
Golpich, M.
Teoh, T.C.
Gholami, K.
Yusof, R.
NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
description N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.
format Article
author Rothan, H.A.
Amini, E.
Faraj, F.L.
Golpich, M.
Teoh, T.C.
Gholami, K.
Yusof, R.
author_facet Rothan, H.A.
Amini, E.
Faraj, F.L.
Golpich, M.
Teoh, T.C.
Gholami, K.
Yusof, R.
author_sort Rothan, H.A.
title NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
title_short NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
title_full NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
title_fullStr NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
title_full_unstemmed NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
title_sort nmda receptor antagonism with novel indolyl, 2-(1,1-dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
publisher Nature Publishing Group
publishDate 2017
url http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf
http://eprints.um.edu.my/19038/
http://dx.doi.org/10.1038/srep45540
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score 13.209306