title: Structural analogs of huperzine A improve survival in guinea pigs exposed to soman.
abstract: 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×LD(50).
authors: Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Chicago, IL 60612, USA.
authors: Hendra
authors: H
authors: Gunosewoyo
authors: Suresh K
authors: SK
authors: Tipparaju
authors: Marco
authors: M
authors: Pieroni
authors: Ying
authors: Y
authors: Wang
authors: Bhupendra P
authors: BP
authors: Doctor
authors: Madhusoodana P
authors: MP
authors: Nambiar
authors: Alan P
authors: AP
authors: Kozikowski
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity; D016019:Survival Analysis
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A; D012999:Soman