Structural analogs of huperzine A improve survival in guinea pigs exposed to soman

Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstra...

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Main Authors: Gunosewoyo, Hendra, Tipparaju, S., Pieroni, M., Wang, Y., Doctor, B., Nambiar, M., Kozikowski, A.
Format: Journal Article
Published: Pergamon 2013
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/35164
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author Gunosewoyo, Hendra
Tipparaju, S.
Pieroni, M.
Wang, Y.
Doctor, B.
Nambiar, M.
Kozikowski, A.
author_facet Gunosewoyo, Hendra
Tipparaju, S.
Pieroni, M.
Wang, Y.
Doctor, B.
Nambiar, M.
Kozikowski, A.
author_sort Gunosewoyo, Hendra
building Curtin Institutional Repository
collection Online Access
description Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose. It is hypothesized that analogs of both (+)- and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents. In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1.2 or 2 × LD50.
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institution Curtin University Malaysia
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spelling curtin-20.500.11937-351642017-09-13T15:32:25Z Structural analogs of huperzine A improve survival in guinea pigs exposed to soman Gunosewoyo, Hendra Tipparaju, S. Pieroni, M. Wang, Y. Doctor, B. Nambiar, M. Kozikowski, A. Acetylcholinesterase Soman Neuroprotection Huperzine A analogs Nerve agent Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose. It is hypothesized that analogs of both (+)- and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents. In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1.2 or 2 × LD50. 2013 Journal Article http://hdl.handle.net/20.500.11937/35164 10.1016/j.bmcl.2012.11.083 Pergamon restricted
spellingShingle Acetylcholinesterase
Soman
Neuroprotection
Huperzine A analogs
Nerve agent
Gunosewoyo, Hendra
Tipparaju, S.
Pieroni, M.
Wang, Y.
Doctor, B.
Nambiar, M.
Kozikowski, A.
Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title_full Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title_fullStr Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title_full_unstemmed Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title_short Structural analogs of huperzine A improve survival in guinea pigs exposed to soman
title_sort structural analogs of huperzine a improve survival in guinea pigs exposed to soman
topic Acetylcholinesterase
Soman
Neuroprotection
Huperzine A analogs
Nerve agent
url http://hdl.handle.net/20.500.11937/35164