Current treatment of
organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone
therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after
soman poisoning. The model allowed the determination of the
therapeutic effects at the short-term of
obidoxime,
atropine and
physostigmine.
Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m.), whereas two higher doses (9 and 18 mg/kg) were less effective on most parameters. Addition of
atropine at 0.03 and 3 mg/kg (i.m.) to the treatment did not improve the
therapeutic effects of
obidoxime alone.
Physostigmine (0.8 mg/kg im) at 1 min after
poisoning increased mortality. Two lower doses (0.1 and 0.3 mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of
obidoxime and
physostigmine shortened the duration of
seizures, if present, from up to 80 min to ~10-15 min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of
physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP
poisoning with a
carbamate, such as
physostigmine, should be carefully re-evaluated.