Inhibition of Acetylcholinesterase and Different ATPases by a Novel Phosphorothionate (RPR-II) in Rat Brain

A novel phosphorothionate (2-butenoic acid-3-(diethoxy phosphinothioyl)-methyl ester (RPR-II), synthesized at the Indian Institute of Chemical Technology, Hyderabad, targets its effect on rat brain acetylcholinesterase (AChE) and Na+–K+, Mg2+, and Ca2+ ATPases, as evident in this investigation. Three subchronic doses 0.014 (low), 0.028 (medium), and 0.042 (high) mg kg−1 were administered to rats daily for a period of 90 days RPR-II caused statistically significant dose- and time-dependent inhibition in brain AChE and also in Na+–K+, Mg2+, and Ca2+ ATPases in both male and female rats after 45 and 90 days of treatment. The low dose was generally insignificant while the medium and high doses were significantly effective. Females were more susceptible than males with regard to brain AChE, Na+–K+, and Mg2+ ATPases, which indicates sexual dimorphism in the treated rats. Interestingly, after 28 days post-treatment, recovery of these enzymes was observed. The relative sensitivities of these enzymes indicated that brain AChE was more sensitive than any of the ATPases, but among the ATPases Na+–K+ ATPase was more susceptible than Ca2+ or Mg2+ ATPases. This compound, besides inhibiting the target of organophosphates, AChE, also inhibited different ATPases, suggesting both synaptic transmission and nerve conduction were affected.