Use of Sugar-Oximes and Other Glycosylated Drugs in Treatment against Organophosphate Poisoning

摘要

During the course of our work, mono-, and bis-sugar oximes as well as glycosylated carbamates were synthesized, analyzed by various spectroscopic techniques and evaluated pharmacologically. We found that the clearance rate of the sugar conjugates was significantly slower and their toxicity was pronouncely lower than that of their parents' compounds. These two properties endow the sugar oximes with improved prophylactic potential as compared to their non-sugar analogues. Moreover, in some cases the sugar oximes exhibited better antidotal properties than their non-cojugated aldoximes. Investigations into the mechanisms underlying the improved properties of the sugar oximes revealed the following: OH-free sugar form is important for the antidotal activity; Propyl bridge between the sugar and the pyridine ring appears to be superior to a direct linkage between the two moieties; Glucose seems to be more efficient than galactose; The glucose transport system does not seem to recognize the sugar oximes. Therefore, sites other than the glucose transporter should be considered as those responsible for their improved pharmacokinetics.