Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review.

Published

Journal Article (Review)

Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i.e. diarrhea, sweating, salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at neuromuscular junctions also can cause paralysis and ultimately peripherally-mediated respiratory arrest which can lead to death via respiratory failure. In addition to its primary action on the cholinergic system, sarin possesses other indirect effects. These involve the activation of several neurotransmitters including gamma-amino-butyric acid (GABA) and the alteration of other signaling systems such as ion channels, cell adhesion molecules, and inflammatory regulators. Sarin exposure is associated with symptoms of organophosphate-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as well as organophosphate-induced endocrine disruption (OPIED). The standard treatment for sarin-like nerve agent exposure is post-exposure injection of atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE reactivator, and diazepam.

Full Text

Duke Authors

Cited Authors

  • Abou-Donia, MB; Siracuse, B; Gupta, N; Sobel Sokol, A

Published Date

  • November 2016

Published In

Volume / Issue

  • 46 / 10

Start / End Page

  • 845 - 875

PubMed ID

  • 27705071

Pubmed Central ID

  • 27705071

Electronic International Standard Serial Number (EISSN)

  • 1547-6898

Digital Object Identifier (DOI)

  • 10.1080/10408444.2016.1220916

Language

  • eng

Conference Location

  • England