title: In vivo protection of diisopropylphosphorofluoridate (DFP) poisoning by three bis-quaternary 2 -(hydroxyimino) -N -(pyridin-3-yl) acetamide derivatives in Swiss mice.
abstract: This study reports efficacy of three bis pyridinium derivatives of 2-(hydroxyimino)- N-(pyridine-3-yl) acetamide in terms of survival, reactivation of brain and serum acetylcholinesterase (AChE) activity in diisopropylphosphorofluoridate (DFP) intoxicated Swiss albino male mice. LD50 of DFP (3.9 mg/kg, s.c.) and new oximes, HNK-102, HNK-106, HNK-111, (282.8, 35.0 and 35.0 mg/kg respectively, i.m.) was determined. Various doses of DFP and oximes as treatment doses with atropine (10 mg/kg, i.p.) were used to determine protection index (PI). For time dependent maximum AChE inhibition, two doses of DFP (0.20 and 2.0 LD50) were chosen. At optimized time i.e. Sixty minutes, IC50 value was calculated as 0.249 and 0.017 LD50 of brain and serum AChE, respectively. Shift of DFP induced brain AChE IC50 curves to right was observed at 0.20 LD50 treatment dose of oximes with respect to 2-PAM. These findings propose that new HNK series of oximes are effective antidote, compared to that of 2-PAM in vivo.
authors.affiliation: Defence Research & Development Establishment Pharmacology and Toxicology Division Gwalior India pravinkumar43&commat;hotmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Defence Research & Development Establishment Pharmacology and Toxicology Division Gwalior India.
authors.forename: D
authors.initials: D
authors.lastname: Swami
authors.affiliation: Defence Research & Development Establishment Process Technology Development Division Gwalior India.
authors.forename: H N
authors.initials: HN
authors.lastname: Karade
authors.affiliation: Defence Research & Development Establishment Process Technology Development Division Gwalior India.
authors.forename: J
authors.initials: J
authors.lastname: Acharya
authors.affiliation: Defence Research & Development Establishment Pharmacology and Toxicology Division Gwalior India.
authors.forename: P C
authors.initials: PC
authors.lastname: Jatav
authors.affiliation: Defence Research & Development Establishment Pharmacology and Toxicology Division Gwalior India.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Defence Research & Development Establishment Pharmacology and Toxicology Division Gwalior India.
authors.forename: M K
authors.initials: MK
authors.lastname: Meena
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D007531:Isoflurophate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D051379:Mice; D010091:Oximes / Q000494:pharmacology; D011041:Poisoning / Q000188:drug therapy / Q000517:prevention & control*; D011220:Pralidoxime Compounds / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D007531:Isoflurophate; D001285:Atropine; D000110:Acetylcholinesterase; C028797:pralidoxime