Protection of human muscle acetylcholinesterase from soman by pyridostigmine bromide

Abstract

In vitro pretreatment of human muscles with PB protected up to 20% of muscle AChE and ameliorated some deleterious effects on endplate physiology induced by soman.

Pyridostigmine bromide protection against acetylcholinesterase inhibition by pesticides

“…The AChE activities of RBCs treated with PB were less inhibited by DFP, PO, DZO, and CPO than those treated with saline (Table 1), demonstrating the protective effect of PB 3,9.…”

“…Gordon et al 10 reported recovery of AChE in PB‐treated lysed human blood after soman ex vivo exposure. But Maselli et al 3 did not find recovery of AChE activity in human muscle treated with PB and soman. Here, RBCs treated with PB and OP pesticides had no recovery of AChE activity, though RBCs treated with PB and DFP did.…”

“…Recent work from U.C. Davis 3 showed that pretreatment with PB protected approximately 20% of the AChE of human intercostal muscle fibers from inhibition by the warfare agent soman and partially protected the electrophysiological responses associated with OP intoxication. Although a “no effect” level for AChE inhibition by OPs has not been quantitatively established, it is likely that protection of even a fraction of the AChE at motor end plates may be sufficient to prevent the worst effects of OP exposures.…”

“…The presence of the carbamate pyridostigmine bromide (PB) has been shown to protect a significant fraction of the AChE from OP inhibition by the nerve gas soman, a potent AChE inhibitor 1,3,4. The mechanism is thought to be a lessening of the effect of the more tightly bound OP by the presence of the more readily hydrolysable carbamate 1.…”

Symptomatische Therapie bei Myasthenia gravis und anderen neuromuskulären Übertragungsstörungen

“…Ausgangspunkt war die Vermutung, dass der kombinierte Einsatz von Pyridostigmin und DEET (sowie Permethrin) w ä hrend des Golfkrieges eine Ursache des sog. Gulf-War-Syndroms gewesen sein k ö nne (Pyridostigminbromid sch ü tzt 20 % der Acetylcholinesterase vor der irreversiblen Bindung durch Giftgas an dieses Enzym [37] ), Untersuchungen an Ratten nach Applikation physiologischer Dosierungen von Pyridostigminbromid und DEET gleichzeitig ergaben deutliche Defi zite in der Beweglichkeit und einen signifi kanten Abfall der Acetylcholinesteraseaktivit ä t im Mittelhirn und Hirnstamm [38] . Untersuchungen am Menschen mit physiologischen Dosen konnten, allerdings nur im Kurzzeitversuch, neurotoxische Sch ä digungen nicht best ä tigen, sie belegten vielmehr -unter zus ä tzlicher Stre ß belastung -sogar eine Besserung neurokognitiver Beeintr ä chtigungen ohne weitere Symptome des Gulf-War-Syndromes (Kopf-und Gelenkschmerzen, M ü digkeit, Adynamie, kognitiven Einbu ß en, Schlafst ö rungen, Ataxie, Atemnot und auch gastrointestinalen Beschwerden [39] ).…”