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

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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Bibliographic Details
Main Authors: Gunosewoyo, Hendra, Tipparaju, S., Pieroni, M., Wang, Y., Doctor, B., Nambiar, M., Kozikowski, A.
Format: Journal Article
Published: Pergamon 2013
Subjects:
Acetylcholinesterase
Soman
Neuroprotection
Huperzine A analogs
Nerve agent
Online Access:http://hdl.handle.net/20.500.11937/35164
Description
Summary: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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