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1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate somaninduced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

A good knowledge of the basic mechanisms of acute toxicity of organophosphorus compounds has lead to the development of specific antidotes able to counteract their acute toxic effects. Unfortunately, there are still some highly toxic organophosphorus compounds, called nerve agents, that are resistant to standard antidotal treatment. Relatively unsatisfactory antidotal treatment of acute poisonings with some nerve agents has prompted studies of pretreatment possibilities that would increase the resistance of organisms exposed to nerve agents. Current protection against nerve agent poisoning is pyridostigmine, but its prophylactic efficacy is rather limited. To increase the effectiveness of pharmacological pretreatment of soman or tabun poisoning, a prophylactic mixture called PANPAL and consisting of pyridostigmine and two anticholinergic drugs – benactyzine and trihexyphenidyle was developed, produced and introduced into the Czech Army to protect soldiers against nerve agent exposure. This review describes the evaluation of the potency of PANPAL to counteract acute soman or tabun poisoning and to increase the therapeutic and neuroprotective efficacy of current post-exposure antidotal treatment in comparison with pyridostigmine given alone as pretreatment., Uvid u osnovne mehanizme akutnog otrovanja organofosfornim spojevima omogućio je razvoj specifičnih protuotrova koji su u stanju poništiti akutno toksično djelovanje otrova. Nažalost još postoje veoma toksični organofosforni spojevi poznati kao živčani otrovi, a koji su otporni na liječenje standardnim protuotrovima. Relativno slabi rezultati dosadašnjeg liječenja akutnog otrovanja živčanim otrovima potaknuli su istraživanje mogućnosti profilakse koja bi povećala otpornost izloženih organizama. Dosada se u te svrhe rabio piridostigmin, ali je njegovo profilaktičko djelovanje prilično ograničeno. Kako bi se povećala djelotvornost profilakse protiv trovanja somanom odnosno tabunom, u oružanim snagama Češke Republike razvijena je kombinirana profilaksa pod nazivom PANPAL, a koja obuhvaća piridostigmin i dva antikolinergika, benaktizin i triheksifenidil. Svrha joj je bolje zaštititi vojnike kod izlaganja živčanim otrovima. Ovaj pregledni rad opisuje testiranje djelotvornosti PANPAL-a protiv akutnog otrovanja somanom odnosno tabunom te poboljšanje terapijskoga i neuroprotektivnog djelovanja kod akutnog otrovanja tabunom odnosno somanom u odnosu na isključivu primjenu piridostigmina kao uobičajene profilakse kod trovanja živčanim agensima.