title: [Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos].
abstract: OBJECTIVE
  In acute organophosphate poisoning the issue of special concern is the appearance of muscle fasciculations and convulsions that cannot be adequately antagonised by the use of atropine and oxime therapy. The aim of this study was to examine atidotal effect of obidoxime or HI-6 combinations with memantine in mice poisoned with soman, dichlorvos or heptenophos.
  
  
  METHODS
  Male Albino mice were pretreated intravenously (iv) with increasing doses of oximes and/or memantine (10 mg/kg) at various times before poisoning with 1.3 LD-50 of soman, dichlorvos or heptenophos, in order to determine the median effective dose and the efficacy half-time. In a separate experiment, cerebral extravasation of Evans blue dye (40 mg/kg iv) was examined after application of memantine (10 mg/kg iv), midazolam (2.5 mg/kg intraperitonealy--ip) and ketamine (20 mg/kg ip) 5 minutes before soman (1 LD-50 subcutaneously--sc).
  
  
  RESULTS
  Coadministration of memantine induced a significant decrease in median effective dose in null time of both HI-6 (7.96 vs 1.79 gmoL/kg in soman poisoning) and obidoxime (16.80 vs 2.75 micromoL/kg in dichlorvos poisoning; 21.56 vs 6.63 micromoL/kg in heptenophos poisoning). Memantine and midazolam succeded to counteract the soman-induced proconvulsive activity.
  
  
  CONCLUSIONS
  Memantine potentiated the antidotal effect of HI-6 against a lethal dose of soman, as well as the ability of obidoxime to antagonize the toxic effects of dichlorvos and heptenophos probably partly due to its anticonvulsive properties.
authors.affiliation: Univerzitet u Beogradu, Farmaceutski fakultet, Katedra za toksikologiju, "Akademik Danilo Soldatovid", Beograd, Srbija. abiljana@pharmacy.bg.ac.rs
authors.forename: Biljana
authors.initials: B
authors.lastname: Antonijević
authors.forename: Milos P
authors.initials: MP
authors.lastname: Stojiljković
authors.forename: Dubravko
authors.initials: D
authors.lastname: Bokonjić
authors.forename: Slavica
authors.initials: S
authors.lastname: Vucinić
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage*; D004006:Dichlorvos / Q000506:poisoning; D004359:Drug Therapy, Combination; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D051379:Mice; D009768:Obidoxime Chloride / Q000008:administration & dosage; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds; D010091:Oximes / Q000008:administration & dosage; D011726:Pyridinium Compounds / Q000008:administration & dosage; D012999:Soman / Q000506:poisoning
chemical_list: D000931:Antidotes; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D004006:Dichlorvos; D012999:Soman; C022870:asoxime chloride; C014022:heptenophos; D008559:Memantine