EFFECT OF ACUTE PHYSOSTIGMINE-HYOSCINE PRETREATMENT ON THE NEUROCHEMICAL CHANGES PRODUCED BY SOMAN IN THE GUINEA-PIG

The protective effects of two dose regimes of the organophosphate pretreatment combination, physostigmine and hyoscine, were assessed on the central neurochemical changes produced following soman intoxication. The lower dose combination (physostigmine 20-mu-g/kg, hyoscine 10-mu-g/kg, s.c.) inhibited brain regional acetylcholinesterase (AChE) by between 13.5 and 37.6% in all regions except the striatum, where there was no statistically significant inhibition. This low dose pretreatment failed to protect a measurable proportion of brain AChE from soman and did not prevent the neurotransmitter changes produces by soman. Signs of intoxication were indistinguishable from those seen with soman alone, however more animals survived longer than 24 h. The higher dose combination (physostigmine 196-mu-g/kg and hyoscine 113-mu-g/kg s.c.) inhibited brain regional AChE by between 56.8 and 67.3%, but had significant effects alone on the levels of ACh and NA. The high dose pretreatment effectively protected 20-30% of the enzyme following soman challenge. This protected enzyme became available as the physostigmine was eliminated from the body after 60-120 min. Animals exhibited mild signs of poisoning, such as hyperactivity and chewing, during the first 30-60 min, after which they recovered. Transmitter changes following soman were completely prevented with high dose pretreatment. Both dose levels of pretreatment decreased lethality but only the high dose, which protected a measurable amount of AChE and prevented neurotransmitter changes, decreased incapacitation.