title: Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos.
abstract: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory.
  
  
  
  In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis.
  
  
  
  K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant.
  
  
  
  These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure.
authors: Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, University Park GL 495 D, 11200 SW 8th St, Miami 33199, Florida. United States.
authors: Dietrich E
authors: DE
authors: Lorke
authors: Bio Science Department, COMSATS Institute of Information Technology, Islamabad. Pakistan.
authors: Syed M
authors: SM
authors: Nurulain
authors: Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, UAE University, 15551 Al Ain. United Arab Emirates.
authors: Mohamed Y
authors: MY
authors: Hasan
authors: Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine; Florida International University; University Park GL 495 D; 11200 SW 8th St, Miami 33199, Florida. United States.
authors: Kamil
authors: K
authors: Kuca
authors: Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine; Florida International University; University Park GL 495 D; 11200 SW 8th St, Miami 33199, Florida. United States.
authors: Georg A
authors: GA
authors: Petroianu
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D010755:Organophosphates / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000008:administration & dosage; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011726:Pyridinium Compounds / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: C513728:4-(aminocarbonyl)-1-(3-(4-((E)-(hydroxyimino)methyl)pyridinium-1-yl)propyl)pyridinium dibromide; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; C000944:dicrotophos
keywords: Carbamates; cholinesterase; cox analysis; dicrotophos; organophosphate; prophylaxis; rat