A comparison of the neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in soman-poisoned rats.
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 soman-induced 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.
Kassa
Jirí
J
Department of Toxicology, Purkynĕ Military Medical Academy, Hradec Králové, Czech Republic. kassa@pmfhk.cz
Krejcová
Gabriela
G
Samnaliev
Ivan
I
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D001285:Atropine / Q000008:administration & dosage; D001535:Benactyzine / Q000008:administration & dosage*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010091:Oximes; D011292:Premedication; D011726:Pyridinium Compounds / Q000008:administration & dosage; D011729:Pyridostigmine Bromide / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*; D014282:Trihexyphenidyl / Q000008:administration & dosage*
D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D004338:Drug Combinations; D018696:Neuroprotective Agents; D010091:Oximes; D011726:Pyridinium Compounds; C416025:panpal; D001535:Benactyzine; D014282:Trihexyphenidyl; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; D011729:Pyridostigmine Bromide