dos Santos_2010_Basic.Clin.Pharmacol.Toxicol_107_768

Reference

Title : In vitro reactivating effects of standard and newly developed oximes on malaoxon-inhibited mouse brain acetylcholinesterase - dos Santos_2010_Basic.Clin.Pharmacol.Toxicol_107_768
Author(s) : Dos Santos AA , dos Santos DB , Dafre AL , de Bem AF , Souza DO , da Rocha JB , Kuca K , Farina M
Ref : Basic Clin Pharmacol Toxicol , 107 :768 , 2010
Abstract :

Malathion is an organophosphate (OP) pesticide whose toxicity depends on its bioactivation to malaoxon. Human malathion poisoning has been treated with oximes (mainly pralidoxime) in an attempt to reactivate OP-inhibited acetylcholinesterase (AChE). However, pralidoxime has shown unsatisfactory therapeutic effects in malathion poisoning and its routine use has been questioned. In this study, we evaluated the in vitro potency of standards and newly developed oximes in reactivating malaoxon-inhibited AChE derived from mouse brain supernatants. Malaoxon displayed a concentration-dependent inhibitory effect on mouse brain AChE (IC(50) = 2.36 microM), and pralidoxime caused a modest reactivating effect (30% of reactivation at 600 microM). Obidoxime and trimedoxime, as well as K047 and K075, displayed higher reactivating effects (from 55% to 70% of reactivation at 600 muM) when compared with pralidoxime. The results show that obidoxime, trimedoxime, K074 and K075 present higher reactivating effects on malaoxon-inhibited AChE under in vitro conditions when compared with pralidoxime. Taking into account the unsatisfactory effects of pralidoxime as antidotal treatment in malathion poisonings, the present results suggest that obidoxime, trimedoxime, K074 and K075 might be interesting therapeutic strategies to reactivate malaoxon-inhibited AChE in malathion poisonings.

PubMedSearch : dos Santos_2010_Basic.Clin.Pharmacol.Toxicol_107_768
PubMedID: 20406208

Related information

Reactivator K074    K075

Citations formats

Dos Santos AA, dos Santos DB, Dafre AL, de Bem AF, Souza DO, da Rocha JB, Kuca K, Farina M (2010)
In vitro reactivating effects of standard and newly developed oximes on malaoxon-inhibited mouse brain acetylcholinesterase
Basic Clin Pharmacol Toxicol 107 :768

Dos Santos AA, dos Santos DB, Dafre AL, de Bem AF, Souza DO, da Rocha JB, Kuca K, Farina M (2010)
Basic Clin Pharmacol Toxicol 107 :768