Obidoxime efficacy

The only two randomized controlled clinical trials performed so far did not result in a final proof of the efficacy of the oximes in the treatment of poisonings induced by the OP insecticides in humans due to methodological problems (Eddleston et al., 2002). However, experimental and clinical experience suggests that among the pyridinium oximes, obidoxime andtrimedoxime, although relatively toxic, could provide reactivation and antidotal protection against most of the OP insecticides. In addition, HI-6 has proved to be effective in the treatment of soman-poisoned animals and safe and effective in patients poisoned with diethoxy OPs. 

Shiloff, J.D., Clement, J.G. (1987). Comparison of serum concentration of the acetylcholinesterase oxime reactivatiors HI-6, obidoxime and PAM to efficacy against sarin (isopropyl methylphosphonofluoridate) poisoning in rats. Toxicol. Appl. Pharmacol. 89 278-80. 

The in vitro test on rat brain homogenate showed that oxime K048 has higher efficacy to reactivate tabun-inhibi-ted AChE than pralidoxime or HI-6, which is comparable with obidoxime. 

Kassa, J., Jun, D., Kuca, K. (2007). A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin and tabun-poisoned rats. J. Enzyme Inhib. Med. Chem. 22 297-300. 

Presently used pralidoxime and obidoxime are also very poor reactivators of cyclosarin-inhibited AChE in vivo (28,29). On the other hand, H oximes seem to be very good reactivators of cyclosarin-inhibited AChE in peripheral and central compartments (30). The efficacy of methoxime to reactivate cyclosarin-in-... 

The ability of pralidoxime, obidoxime and methoxime to reactivate sarin-inhibited AChE in rat diaphragm and brain is relatively low although methoxime seems to be better reactivator of sarin-inhibited AChE in vivo than expected on the basis of its in vitro reactivation potency (23). H oximes (HI-6, HLp-7) are very efficacious reactivators of sarin-inhibited AChE especially in diaphragm (23). However, they also seem to be good reactivators of sarin-inhibited AChE in the central compartment in spite of their quaternary structure that limits their penetration across the blood-brain barrier. 

The efficacy of oximes against sarin depends on the species of the experimental animals. While most experiments show pralidoxime and obidoxime to be of comparable, moderate effectiveness in mice and rats, high effectiveness of both oximes was observed in guinea pigs. The oxime HI-6 seems to be more efficacious than currently used oximes (pralidoxime and obidoxime) in mice and rats but its efficacy does not reach the effectiveness of pralidoxime and obidoxime in guinea pigs (Table 4). 

Kassa, J., A comparison of the efficacy of new asymmetric bispyridinium oxime BI-6 with other oximes (obidoxime, HI-6) against soman in rats, Hum. Exp. Toxicol., 17, 331-335,1998. 

Clement, J.G., Shiloff, J.D., and Gennings, C., Efficacy of the combination of acetylcholinesterase reactivators, HI-6 and obidoxime, against tabun and soman poisoning in mice, J. Chromatogr., 389, 87-94, 1987. 

Kassa, J., Comparison of efficacy of two oximes (HI-6 and obidoxime) in soman poisoning in rats, Toxicology, 101,167-174,1995. 

Bcs.scr, R., Weilemann, L. S.. and Gutmann, I,. (1995). Efficacy of obidoxime in human organophosphoms poisoning Determination by neuromuscular transmission studie.s. Muscle Nerve 18, 1.5-22. 

In three studies reviewed by FAO/WHO (1994) on phosalone and 2-PAM methylsulfate in mice, P2S in rats, and obidoxime in mice, all appeared effective, although various aspects of the design of the. studies were not optimal. Oximes (PAM or obidoxime) in combination with atropine were successful in rats experimentally poisoned with pyrazophos, and there was some indication that repeated dosing was required for optimal antidotal efficacy (FAO/WHO, 1993). In a rat study of experimental terbufos poisoning, little benefit was observed from PAM and atropine (FAO/WHO, 1991). In rat studies on triazophos, combinations of atropine. sulfate and 2-PAMI or atropine sulfate and obidoxime were successful as experimental therapies (FAO/WHO, 1994). The effects of oximes in profenofas-poisoned chicks and mice were reported to be limited, as expected, although atropine was effective (FAO/WHO, 1991). 

Theirmann, H., Worek, R, Eyer, R, 2009. Comments on "efficacy of two new asymmetric bispyridinium oximes (K-27 and K-48) in rats exposed to diisopropylfluorophosphate comparison with pralidoxime, obidoxime, trim-edoxime, methoxime, and HI 6". Toxicol. Mech. Methods 19 (4), 334. 

M. J. A. Joosen, M. J. van der Schans and H. P. M. van Helden, Percutaneous exposure to the nerve agent VX efficacy of combined atropine, obidoxime and diazepam treatment, Chem.-Biol Interact., 2010,188,255. 

Obidoxime is normally second line freotment for nerve agent treatment in UK after pralidoxime. However, it is more efficacious with known Tabun toxicity or when pralidoxime does not work. 

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