The protective action of eseroline--(3aS,8aR)-1,2,3,3a,8,8a-hexahydro-1,3 a, 8-trimethyl-pyrrolo[2,3-b]indol-5-ol--
salicylate against (
DFP) diisopropyl
fluorophosphate and
carbamate poisoning of
cholinesterases (
ChEs) has been examined in-vitro with human erythrocytes and purified preparations of electric eel
acetylcholinesterase (AChE) and of horse serum
butyrylcholinesterase (BuChE), and in-vivo using mice.
Eseroline afforded 50% protection (ED 50) of erythrocyte AChE against inactivation by 1 microM
DFP,
physostigmine or
neostigmine, at concentrations of 4.3, 22 and 23.5 microM, respectively, while for eel AChE protection against 10 and 30 microM
DFP, 0.3 and 1 microM
physostigmine and 1 microM
neostigmine the
eseroline ED 50 values were 0.3, 0.4, 0.7, 1.9 and 5.6 microM, respectively. On the other hand, up to 0.3 mM
eseroline did not appreciably affect the inhibitory action of the same drugs on horse serum BuChE.
Eseroline concentrations in the range 0.1-1 mM were able to reactivate 20-42% of erythrocyte AChE previously inhibited by 100 microM
physostigmine, but failed to reactivate the
DFP (10 microM)-pretreated
enzyme to any extent. Finally,
eseroline salicylate injected into mice (10 mg kg-1 s.c.) protected an average of 82 and 26% of the animals against lethal doses of
DFP (7 mg kg-1 s.c.) and
physostigmine sulphate (1 mg kg-1 i.p.) respectively, which were administered 15 min later. These results indicate that the protective activity of
eseroline correlates well with its own anti-ChE profile, and that the effectiveness of the protection depends largely on the rate of AChE inhibition by the agents used to inactivate the
enzyme.