Organophosphates (OPs) represent a class of highly toxic compounds that includes nerve agents, insecticides and pesticides. The biological effects of OPs are exerted by reversible or irreversible inhibition of acetylcholinesterase (AChE), which results in attenuation of the catalysed hydrolysis of acetylcholine (ACh) and excessive accumulation of extracellular ACh. The ensuing hyperactivation of ACh receptors results in various toxic effects including hypersecretions, convulsions, respiratory distress, coma and ultimately death. Current emergency treatment of acute OP poisoning consists of combined administration of an AChE reactivator (an oxime), a muscarinic ACh receptor antagonist (e.g. atropine) and an anticonvulsant (e.g. diazepam). For several reasons, a critical re-evaluation of the efficacy of the current treatment of OP poisoning is necessary. First, chemical warfare is still a realistic threat in many parts of the world; because chemical warfare agents now appear to be easily available to terrorists, the unprotected civil population is at risk. Second, great difficulties have been encountered on treating heavily pesticide-poisoned victims, despite oxime treatment and administration of high dosages of atropine 1 Willems J.L et al. Arch. Toxicol. 1993; 67: 79-84 Crossref PubMed Scopus (83) Google Scholar . Moreover, recent experiments using nerve-gas-poisoned primates demonstrated that current treatment did not prevent neuronal brain damage and the resulting incapacitation 2 Dawson R.M J. Appl. Toxicol. 1994; 14: 317-331 Crossref PubMed Scopus (316) Google Scholar , 3 Van Helden H.P.M Busker R.W Melchers B.P.C Bruijnzeel P.L.B Arch. Toxicol. 1996; 70: 779-786 Crossref PubMed Scopus (163) Google Scholar , 4 Lallement G et al. Arch. Toxicol. 1998; 72: 84-92 Crossref PubMed Scopus (59) Google Scholar , 5 Shih T.M McDonough Jr, J.H J. Appl. Toxicol. 1997; 17: 255-264 Crossref PubMed Scopus (152) Google Scholar . One main drawback of current treatment is that it is not generic: treatment is not equally effective against all OPs, which suggests that the toxic compound must be identified before the best available treatment can be applied 2 Dawson R.M J. Appl. Toxicol. 1994; 14: 317-331 Crossref PubMed Scopus (316) Google Scholar , 3 Van Helden H.P.M Busker R.W Melchers B.P.C Bruijnzeel P.L.B Arch. Toxicol. 1996; 70: 779-786 Crossref PubMed Scopus (163) Google Scholar , 6 Worek F Widmann R Knopff O Szinicz L Arch. Toxicol. 1998; 72: 237-243 Crossref PubMed Scopus (126) Google Scholar . Thus, improved, more generic therapies are required to accomplish sufficient protection against OP poisoning.