title: Neurosteroids for the potential protection of humans against organophosphate toxicity.
abstract: This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent-induced life-threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABAAreceptors, benzodiazepine resistance, and brain injury. Neurosteroid-sensitive extrasynaptic GABAAreceptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas. reddy@medicine.tamhsc.edu.
authors.forename: Doodipala Samba
authors.initials: DS
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D062025:Organophosphate Poisoning / Q000175:diagnosis / Q000517:prevention & control*; D010755:Organophosphates / Q000633:toxicity*; D013226:Status Epilepticus / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010755:Organophosphates
keywords: benzodiazepine; nerve agent; neuroactive steroid; neurosteroid; organophosphate