Efficacies of Atropine/2-PAM and Atropine/HI-6 in Treating Monkeys Intoxicated with Organophosphonate Nerve Agents

Abstract

The efficacies of atropine (ATR)/ 2-PAM and ATRl HI-6 in treating male rhesus monkeys injected with the neurotoxic organophosphonate (OP) agents GA, GB, GD, GF, or VX were compared. Experiments were conducted using no more than 8 monkeys per OP and treatment regimen. Doses were selected using a modified up-and-down experimental design, challenging one monkey per day per OP and treatment. Results were used to approximate the median lethal dose (MLD) for groups of treated monkeys or monkeys given only a vehicle following challenge with an OP. Mortality and signs of intoxication with each treatment were statistically compared. Doses of 2-PAM (25.7 mgl kg) or HI-6 (50 mgl kg) and atropine (0.4 mg free base! kg) were given in a single intramuscular (IM) injection 1 min following challenge with an OP. Strong and well-defined relationships between agent dose and 10-h lethality were observed in untreated animals. The 10-h IM OP MLDs for untreated monkeys were estimated to be 80, 43, 8.0, 22, and 7.4 μg/kg for GA, GB, GD, GF, and VX, respectively. No statistical differences w ere found between AT Rl 2-PAM and AT Rl HI-6 treatment efficacies in preventing lethality for any of the OPs. Both oxime combinations appear to provide protection against a 2 × 10-h MLD of GA, GF, or VX; only