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

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
Published: Nature Publishing Group 2017
Subjects:
Q Science (General)
R Medicine
Online Access:http://dx.doi.org/10.1038/srep45540
http://dx.doi.org/10.1038/srep45540
http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf
id um-19038
recordtype eprints
spelling um-190382018-08-30T06:04:59Z 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 http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf http://dx.doi.org/10.1038/srep45540 Rothan, H.A.; Amini, E.; Faraj, F.L.; Golpich, M.; Teoh, T.C.; Gholami, K.; 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 <http://eprints.um.edu.my/view/publication/Scientific_Reports.html>, 7 (1). p. 45540. ISSN 2045-2322 http://eprints.um.edu.my/19038/
repository_type Digital Repository
institution_category Local University
institution University Malaya
building UM Research Repository
collection Online Access
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://dx.doi.org/10.1038/srep45540
http://dx.doi.org/10.1038/srep45540
http://eprints.um.edu.my/19038/1/NMDA_receptor_antagonism_with_novel_indolyl.pdf
first_indexed 2018-09-06T06:55:53Z
last_indexed 2018-09-06T06:55:53Z
_version_ 1610840228739678208

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