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. © 2012 Elsevier Ltd. All rights reserved.
Structural analogs of huperzine A improve survival in guinea pigs exposed to soman / Gunosewoyo, Hendra; Tipparaju, Suresh K.; Pieroni, Marco; Wang, Ying; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.; Kozikowski, Alan P.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 23:5(2013), pp. 1544-1547. [10.1016/j.bmcl.2012.11.083]
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