ABSTRACT

The classic treatment of cyanide intoxication is based on the ability of sodium nitrite to generate methemoglobin, a cyanide scavenger, and sodium thiosulfate, a substrate for cyanide metabolism.1 This antidotal combination is effective when the patient is treated immediately after poisoning. However, there is a clear need for a more effective, safer antidote that can be administered in the field. The present study was initiated in an effort to develop an in vitro assay that could screen a large number of potential antidotes in a cost-effective manner and minimize the use of animals. Since the primary target organ of cyanide is the central nervous system, the strategy was to develop a more comprehensive understanding of cyanide’s action on the nervous system

and then to develop a mechanistic based screen in a clonal cell line. Validation of the assay would be based on correlating animal data with that obtained in the screen battery.