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Title: Novel neuroprotective effects with O-benzyl derivative of pralidoxime in soman-intoxicated rodents
Authors: Loke, W.-K.
Sim, M.-K.
Go, M.-L. 
Keywords: Acetylcholine
Anticonvulsant effect
Non-reactivation effect
Pralidoxime derivative
Sedative effect
Soman poisoning
Issue Date: 3-Oct-2005
Citation: Loke, W.-K., Sim, M.-K., Go, M.-L. (2005-10-03). Novel neuroprotective effects with O-benzyl derivative of pralidoxime in soman-intoxicated rodents. European Journal of Pharmacology 521 (1-3) : 59-69. ScholarBank@NUS Repository.
Abstract: Pharmacological properties of oxime reactivators, not related to its ability to regenerate or reactivate nerve agent-inhibited acetylcholinesterase located at nerve synapses, have been reported to be important in protecting against poisoning by the nerve agent soman. Such non-reactivation effects have thus far been associated only with bispyridinium oximes. This study investigated the possibility of creating similar non-reactivation therapeutic effects in the mono-pyridinium ring oxime, pralidoxime (2-PAM) through attachment of alkyl groups of increasing chain length to the oxime functional group. Of the 4 derivatives investigated, only the O-benzyl derivative displayed strong sedative effects in mice and mitigated the development of motor convulsions following soman challenge (1.8 × LD50, subcutaneous). Anticonvulsant effects of this compound were enhanced by co-administration of a non-anticonvulsant dose of atropine sulfate. Administration of equivalent amount of other O-derivatives of pralidoxime failed to elicit similar anticonvulsant actions. Electroencephalographic (EEG) and histopathological studies using the rat model, intoxicated with a lethal dose (1.6 × LD50, s.c.) of soman, confirmed O-benzyl derivative neuroprotective capabilities when used as a pretreatment drug. Microdialysis studies revealed that its neuroprotective effect is related to its ability to attenuate soman-induced increase in acetylcholine. © 2005 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmacology
ISSN: 00142999
DOI: 10.1016/j.ejphar.2005.07.033
Appears in Collections:Staff Publications

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