title: In vivo protection studies of bis-quaternary 2-(hydroxyimino)- N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice.
abstract: The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.
authors.affiliation: 1 Pharmacology and Toxicology Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 1 Pharmacology and Toxicology Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: D
authors.initials: D
authors.lastname: Swami
authors.affiliation: 1 Pharmacology and Toxicology Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: D P
authors.initials: DP
authors.lastname: Nagar
authors.affiliation: 1 Pharmacology and Toxicology Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: 2 Process Technology Development Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: J
authors.initials: J
authors.lastname: Acharya
authors.affiliation: 2 Process Technology Development Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Karade
authors.affiliation: 1 Pharmacology and Toxicology Division, Defence Research & Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: R
authors.initials: R
authors.lastname: Yadav
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000627:therapeutic use; D008297:Male; D051379:Mice; D000067397:Nerve Agents / Q000633:toxicity; D062025:Organophosphate Poisoning / Q000188:drug therapy; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D000067397:Nerve Agents; D010755:Organophosphates; D010091:Oximes; D012999:Soman; C009374:tabun
keywords: HNK oximes; HNK-102; in vivo AChE IC50; soman; tabun