Zorbaz_2020_Period.biol_121122_35

Organophosphate (OP) compounds remain a great threat for humans because they are used as pesticides or misused as chemical warfare nerve agents. Their mechanism of toxicity involves the irreversible inhibition of the acetylcholinesterase (AChE) enzyme important in the control of cholinergic neurotransmission at the periphery and in the brain. An available pharmacological treatment are oxime compounds, that are reactivators of OP-inhibited AChE. However, oximes are not equally effective for every possible OP and they cross the blood-brain barrier (BBB) poorly. Novel oximes are being designed and synthesized at a high rate and scale and their pharmacological efficiency is being addressed mostly with the in vitro reactivation assay. Nevertheless, only few newly synthesized oximes have shown comparable or better pharmacological properties than the ones developed more than 65 years ago beacuse oxime potential to act as efficient antidote in vivo depends on its pharmacokinetic and neuropharmacokinetics profile. This paper provides an overview of all the important aspects that should be accounted for in the search for a centrally active oxime. Furthermore, it lists the most important BBB oxime delivery strategies employed until now, and the available pharmacokinetic data on old and new oximes