Method of treating organophosphate intoxication by administration of neurosteroids

Abstract

The present invention provides new compositions and methods for treating and/or reversing organophosphate intoxication, manifested by both cholinergic and non-cholinergic crisis, in a mammal resulting from exposure to organophosphate compounds. The neurosteroidal compounds of this invention are those having the general structural formula of pregnane, androstane, 19-norandrostanes, and norpregnane with further moieties as defined herein. These compounds include, but are not limited to, ganaxolone, pregnanolone, and androstanediol and their analogs, salts and prodrugs. The present invention further relates to combining a therapeutically effective amount of a neurosteroidal compound with a standard organophosphate antidote (e.g. atropine, pralidoxime). The data suggests that neurosteroids are effective or more effective than benzodiazepines, whether given earlier or later than 40-min (up to several hours) after organophosphate compound exposure. Neurosteroids are effective to attenuate long-term neuropsychiatric deficits caused by organophosphate exposure.