title: Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats.
abstract: The progression of epileptiform activity following soman (GD) exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus, which may lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties, which conceptually may be a beneficial therapeutic approach to the treatment of nerve agent exposure. In the present study, rats were exposed to 1.2 LD50 GD or saline, treated with atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure, and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc) and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD exposure, performance was evaluated using a battery of behavioral tests to assess motor coordination and function, sensorimotor gating, and cognitive function. Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure activity, neuropathological damage, and cognitive deficits compared to diazepam alone, but did not attenuate the GD-induced sensorimotor gating impairment. These findings show that physiological, behavioral, and neuropathological effects of GD exposure can be attenuated by treatment with caramiphen as an adjunct to therapy, even if administration is delayed to 30min after seizure onset.
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: M K
authors.initials: MK
authors.lastname: Schultz
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: L K M
authors.initials: LK
authors.lastname: Wright
authors.affiliation: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, United States.
authors.forename: M
authors.initials: M
authors.lastname: de Araujo Furtado
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: M F
authors.initials: MF
authors.lastname: Stone
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: M C
authors.initials: MC
authors.lastname: Moffett
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: N R
authors.initials: NR
authors.lastname: Kelley
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: A R
authors.initials: AR
authors.lastname: Bourne
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Lumeh
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: C R
authors.initials: CR
authors.lastname: Schultz
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States.
authors.forename: J E
authors.initials: JE
authors.lastname: Schwartz
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States. Electronic address: lucille.a.lange.civ@mail.mil.
authors.forename: L A
authors.initials: LA
authors.lastname: Lumley
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D003517:Cyclopentanes / Q000627:therapeutic use*; D003975:Diazepam / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010091:Oximes / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012999:Soman / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D002800:Cholinesterase Inhibitors; D003517:Cyclopentanes; D010091:Oximes; D011726:Pyridinium Compounds; C000595810:caramiphen edisylate; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; D003975:Diazepam
keywords: Anticonvulsant; Behavior; Caramiphen; Chemical warfare nerve agents; Rats; Soman