Disease relevance of Cyclohexyl methylphosphonofluoridate

• Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerve agents effectively [1].
• Inhalation toxicity of Cyclosarin (GF) vapor in rats as a function of exposure concentration and duration: potency comparison to sarin (GB) [2].
• The current studies estimated effective (miosis) concentrations of the nerve agents' sarin (GB) and cyclosarin (GF) as a function of exposure duration in the Gottingen minipig and determined dependency of the median effective dosage (ECT50) over time [3].
• Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings [4].

High impact information on Cyclohexyl methylphosphonofluoridate

• Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl)methylphosphonothioate (VX), and O-isobutyl S-(2-diethylamino)ethyl)-methyl phosphonothioate (VR) [5].
• The greatest inhibition was observed for the O-cyclohexyl methylphosphonyl-2PAM derivative (4.0 x 10(9)M(-1)min(-1); mouse AChE) and is 10-fold higher than the k(i) of cyclosarin [6].
• Effects of low-level inhalation exposure to cyclosarin on learned behaviors in Sprague-Dawley rats [7].
• Mortality dose-response curves for several OP compounds (i.e., VX, soman, cyclosarin, sarin, tabun, diisopropylfluorophosphate and paraoxon) exhibited steep probit slopes (> 9.6) in guinea pigs [8].
• On the other hand, only HI-6 is able to reactivate satisfactorily cyclosarin-inhibited AChE [9].

Chemical compound and disease context of Cyclohexyl methylphosphonofluoridate

• Oximes in combination with atropine, are an integral part of the treatment of acute intoxications with organophosphorus insecticides or with the nerve agents such as tabun, sarin, soman, cyclosarin or VX [10].
• The toxicity of cyclohexyl methylphosphonofluoridate (GF-agent; cyclosarin) and therapeutic efficacy of four oximes (trimedoxime, methoxime, obidoxime and HI-6) in combination with atropine or benactyzine (BNZ) was studied in mice [11].
• The relative potencies of these compounds, as well as soman, cyclohexyl methylphosphonofluoridate, and diisopropyl fluorophosphate, as inhibitors of AChE in primary cultures of mouse embryo neurons, correlated with their in vivo toxicities [12].
• Mammalian paraoxonase (PON1) was found to be more active than Pseudomonas diminuta OP hydrolase (OPH) and squid O,O-di-isopropyl fluorophosphatase (DFPase) in detoxifying cyclosarin (O-cyclohexyl methylphosphonofluoridate) and soman (O-pinacolyl methylphosphonofluoridate) [13].

Biological context of Cyclohexyl methylphosphonofluoridate

• To give more insight into the inhibition, reactivation and aging kinetics, human acetyl-(AChE) and butyrylcholinesterase (BChE) were inhibited by cyclosarin (k2 of 7.4 and 3.8 x 10(8) M(-1) min(-1), respectively; pH 7.4, 37 degrees C) and reactivated with obidoxime, pralidoxime and three experimental oximes [14].
• As stereoisomers of cyclosarin and soman differ significantly in their acetylcholinesterase-inhibiting potency, we actually measured the hydrolysis of the more toxic stereoisomers [13].
• Generation, sampling, and analysis for low-level GB (Sarin) and GF (Cyclosarin) vapor for inhalation toxicology studies [15].

Anatomical context of Cyclohexyl methylphosphonofluoridate

• The reactivating properties of the two salts were compared on human erythrocyte AChE inhibited with paraoxon, sarin, cyclosarin and agent VX [16].

Associations of Cyclohexyl methylphosphonofluoridate with other chemical compounds

• Obidoxime and pralidoxime were weak reactivators of cyclosarin-inhibited AChE [17].
• The efficacy of oxime (HI-6, toxogonin or PAM Cl) therapy against GF (cyclohexyl methylphosphonofluoridate) poisoning was assessed in mice [18].
• A comparison of the efficacy of a bispyridinium oxime--1,4-bis-(2-hydroxyiminomethylpyridinium) butane dibromide and currently used oximes to reactivate sarin, tabun or cyclosarin-inhibited acetylcholinesterase by in vitro methods [19].
• Nerve agents (sarin, soman, cyclosarin, tabun and VX agent) and pesticides (paraoxon, chlorpyrifos, TEPP) represent extremely toxic group of organophosphorus compounds (OPCs) [20].

Gene context of Cyclohexyl methylphosphonofluoridate

• GC/pulsed flame photometer detector analysis, compared with assay of residual acetylcholinesterase inhibition, displayed stereoselective hydrolysis of cyclosarin, soman, and IMP-pNP, indicating that PON1 is less active toward the more toxic optical isomers [13].
• K033 is sufficient reactivator of cyclosarin-inhibited AChE [21].

Analytical, diagnostic and therapeutic context of Cyclohexyl methylphosphonofluoridate

• Cyclosarin caused a marked statistically significant change in most of the neurobehavioral parameters (FOB) at 24 h and 7 days after exposure, compared to the saline control group [22].

References