Efficacy of prophylaxis and treatment against soman intoxication

The efficacy against lethality and post-intoxication incapacitation after 2x LD50 soman of different subacute pretreatment scenarios of 12 days was tested with or without post-intoxication therapy in guinea pigs. These pretreatment regimes were 1) the currently used pretreatment with pyridostigmine (PYR, 0.04 mg/kg/hr), 2) the combination of physostigmine (PHY, 0.025 mg/kg/hr) with the muscarinic receptor antagonist scopolamine (SCO, 0.018 mg/kg/hr), and 3) the combination of PHY with the anti-Parkinson drug procyclidine (PC, 3 mg/kg, sc). The post-intoxication therapy consisted of HI-6 (21.4 mg/kg, im), atropine sulphate (AS, 0.085 mg/kg, im), and diazepam (DZP, 0.21 mg/kg, im). Different behavioral and observational read-out systems were used to elucidate objectively the severity of soman induced incapacitation.
There were no big differences in the symptomatology between the animals pretreated with PHY+SCO or with PYR. On the other hand, animals pretreated with PHY+PC did not show worse symptoms as was found in the other groups. In some cases the post-intoxication therapy was even not necessary.
Although the symptomatology between the animals treated with PHY+SCO and PYR were comparable the effects on incapacitation and survival were not comparable: all animals pretreated with PYR and the post- intoxication therapy did not perform in the behavioral test systems and died within 24 hours. This was the same result as what was found in unpretreated animals which were treated only with the post-intoxication therapy. The mortality in animals pretreated with PHY+SCO was 25%. The addition of a post intoxication therapy in PHY+SCO pretreated animals did not improve the efficacy. On the other hand, animals pretreated with PHY+PC all survived even without post-intoxication therapy. The performance in the behavioral test systems was similar for animals retreated with PHY+SCO or PHY+PC. Animals without any treatment, besides soman, all died within one hour.
Prophylaxis with the combination of PHY and SCO seems to be a good alternative for the current PYR pretreatment, in particular since this pretreatment showed no side effects in previous studies with guinea pigs and marmoset monkeys and protects efficiently against 2x LD50 soman. The addition of PC to PHY, instead of SCO, augments the efficacy of the pretreatment against soman poisoning. In that case an additional post-intoxication therapy is not necessary. The combination of PHY + PC seems to be very promising and should be further investigated.