PYR, a reversible AChE inhibitor, is the current pretreatment against OP intoxication. However, PHY in the presence or absence of SCO on one side, and HUP on the other side, could be considered as potential substitutes for PYR. In the present study, the effects of the subchronic administration of these different current or potential pretreatments on the BBB permeability for blood-borne albumin and on the activity of the blood and central cholinesterases are comparatively evaluated in guinea-pigs. Altogether, although some marginal disruptions of BBB are detected, the different current or potential pretreatments studied seem to have a total innocuousness on the permeability of the BBB for proteins. Finally, at the light of its particular inhibitory effects on blood and central cholinesterases, HUP, compared to the other drugs, seems to be the optimal candidate to be used as pretreatment against OP poisoning.