Effects of subchronic pyridostigmine pretreatment on the toxicity of soman

Abstract

The effect of subchronic pyridostigmine pretreatment on the toxicity of soman, in the absence of supporting therapy (atropine, oxime, and (or) anticonvulsant), as well as its effect on muscarinic cholinoceptor binding characteristics was assessed in the rat. Pretreatment with pyridostigmine by means of an implanted Alzet osmotic minipump for a 5-day total exposure dose of 12 mg/kg inhibited whole blood acetylcholinesterase activity by 73%. This pyridostigmine pretreatment lowered the soman LD50 from 104 micrograms/kg in control animals to 82 micrograms/kg. In addition, the time to onset of soman-induced convulsions in pyridostigmine pretreated animals was significantly (p less than 0.001) reduced. Pyridostigmine pretreatment produced no significant effect on muscarinic cholinoceptor binding in brain or ileum. Lower doses of pyridostigmine pretreatment inhibited acetylcholinesterase activity (65 and 25%); however, LD50 and time to onset of convulsions following soman (140 micrograms/kg) were not significantly different from controls.

Quantification of pralidoxime (2‐PAM) in urine by ion pair chromatography‐diode array detection: application to in vivo samples from minipig

“…It has been shown that therapeutic concentrations of 2-PAM are quite high in rat plasma and serum (1.4-5.5 mg/ml; [27] up to 100 mg/ml; [26] 0.7-3.3 mg/ml [28] ), in sheep plasma (up to 7 mg/ ml, [33] and in human plasma and serum (0.5-3 mg/ml; [23,24] 3-6 mg/ml; [25] 3-15 mg/ml [12,13] ). Concentrations in human urine were more than 100-times higher (250-2000 mg/ml [20] ).…”

“…Therefore, the DAD was set to these values for quantitative measurement under standard conditions. However, earlier reports applied a broad variety of different wavelengths, for example, 262, 270, 280, 290, 294, and 300 nm [13,28,29,[34][35][36] to detect 2-PAM quantitatively. These values may be due to different HPLC solvent components, the pH used, or simply to non-optimum settings.…”

“…Several methods have been introduced including paper chromatography, [6] ion metal affinity chromatography (IMAC), [19] capillary zone electrophoresis (CZE), [20,21] cation exchange chromatography, [13,22] and reversed-phase chromatography (RPC). [23,24] But most frequently ion pair chromatography (IPC) coupled to electrochemical detection (ECD), [25,26] radio detection (RD), [27] and UV detection [14,28,29] has been applied. For a detailed overview, see the review on 2-PAM quantification in this issue.…”

Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

“…This study shows that PB above 40 mg/kg is toxic in concern to hematology, serum biochemical parameters and physiology of liver and kidney when administered for over one month continuously. It is important to realize that PB is not an antidote and it has no value when administered after nerve-agent exposure [44]. PB is an antidote enhancer rather than a pretreatment capable of acting by itself in the absence of antidotes [45].…”

Development of Miotic Cross-Tolerance Between Pyridostigmine and Sarin Vapor

“…It has been shown previously that a 5-d exposure to PB did not alter muscarinic receptor binding in the brain or ileum of rat. 22 Additionally, the cholinesterase inhibitor soman has been shown to result in miotic tolerance without decreasing the number of muscarinic receptors on the pupillary sphincter muscle. 17 Thus, it is not likely that a decreased number of muscarinic receptors, secondary to internalization or decreased synthesis, is responsible for the observed tolerance.…”