Abou-Donia Mohamed B, Siracuse Briana, Gupta Natasha, Sobel Sokol Ashly
a Department of Pharmacology and Cancer Biology , Duke University , Durham , NC , USA.
Crit Rev Toxicol. 2016 Nov;46(10):845-875. doi: 10.1080/10408444.2016.1220916. Epub 2016 Oct 5.
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.
沙林（GB，O - 异丙基甲基膦酰氟）是一种强效有机磷神经毒剂，能不可逆地抑制乙酰胆碱酯酶（AChE）。随后，中枢神经系统（CNS）中乙酰胆碱（ACh）的蓄积会引发癫痫发作，剂量足够时会导致中枢介导的呼吸骤停。ACh在周围自主神经突触处的蓄积会导致中毒的外周体征以及毒蕈碱和烟碱受体的过度刺激，这被称为“胆碱能危象”（即腹泻、出汗、流涎、瞳孔缩小、支气管收缩）。接触高剂量沙林可导致震颤、癫痫发作和体温过低。更严重的是，ACh在神经肌肉接头处的蓄积还可导致麻痹，并最终导致外周介导的呼吸骤停，进而因呼吸衰竭而死亡。除了对胆碱能系统的主要作用外，沙林还具有其他间接作用。这些作用包括激活多种神经递质，如γ - 氨基丁酸（GABA），以及改变其他信号系统，如离子通道、细胞黏附分子和炎症调节因子。接触沙林与有机磷诱导的迟发性神经毒性（OPIDN）和有机磷诱导的慢性神经毒性（OPICN）症状有关。此外，沙林还涉及毒性和免疫毒性作用以及有机磷诱导的内分泌干扰（OPIED）。针对沙林类神经毒剂暴露的标准治疗方法是暴露后注射阿托品（一种毒蕈碱受体拮抗剂），同时注射肟（一种AChE复活剂）和地西泮。
