title: Protection by a transdermal patch containing physostigmine and procyclidine of soman poisoning in dogs.
abstract: The prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against soman intoxication was evaluated using dogs. Female beagle dogs (body weights 9-10 kg) were shaved on the abdominal side, attached with a matrix-type patch (7x7 cm) containing 1.5% of physostigmine plus 6% procyclidine for 2 days, and challenged with subcutaneous injection of serial doses (2-10 LD50) of soman. Separately, in combination with the patch attachment, atropine (2 mg/dog) plus 2-pralidoxime (600 mg/dog) or atropine plus 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI-6, 500 mg/dog) were injected intramuscularly 1 min after soman poisoning. The LD50 value of soman was determined to be 9.1 microg/kg, and high doses (> or = 1.4 LD50) of soman induced salivation, emesis, defecation and diarrhea, tremors and seizures, and recumbency of dogs, leading to 100% mortality in 24 h. The prophylactic patch, which led to mean 18.5-18.8% inhibition of blood cholinesterase activity by physostigmine and mean 7.9-8.3 ng/ml of blood concentration of procyclidine, exerted a high protection ratio (4.7 LD50), in comparison with relatively-low effects of traditional antidotes, atropine plus 2-pralidoxime (2.5 LD50) and atropine plus HI-6 (2.7 LD50). Noteworthy, a synergistic increase in the protection ratio was achieved by the combination of the patch with atropine plus HI-6 (9 LD50), but not with atropine plus 2-pralidoxime (5 LD50). In addition, the patch system markedly attenuated the cholinergic signs and seizures induced by soman, especially when combined with atropine plus HI-6, leading to elimination of brain injuries and physical incapacitation up to 6 LD50 of soman poisoning. Taken together, it is suggested that the patch system containing physostigmine and procyclidine, especially in combination with atropine and HI-6, could be a choice for the quality survival from nerve-agent poisoning.
authors.affiliation: Biomedical Section, Agency for Defense Development, Yuseong P.O. Box 35-1, Daejeon 305-600, Republic of Korea.
authors.forename: Wang-Soo
authors.initials: WS
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Cho
authors.forename: Jee-Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Zai-Zhi
authors.initials: ZZ
authors.lastname: Huang
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Ehn-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Sunhee
authors.initials: S
authors.lastname: Shin
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Nam
authors.forename: Jong-Koo
authors.initials: JK
authors.lastname: Kang
authors.forename: Seock-Yeon
authors.initials: SY
authors.lastname: Hwang
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D005260:Female; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010091:Oximes; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D011352:Procyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D012999:Soman / Q000506:poisoning*
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D012999:Soman; D010830:Physostigmine; D011352:Procyclidine; C022870:asoxime chloride