Potency of irritation by benzylidenemalononitriles in humans correlates with TRPA1 ion channel activation.

ABSTRACT: We show that the physiological activity of solid aerosolized benzylidenemalononitriles (BMNs) including 'tear gas' (CS) in historic human volunteer trials correlates with activation of the human transient receptor potential ankyrin 1 ion channel (hTRPA1). This suggests that the irritation caused by the most potent of these compounds results from activation of this channel. We prepared 50 BMNs and measured their hTRPA1 agonist potencies. A mechanism of action consistent with their physiological activity, involving their dissolution in water on contaminated body surfaces, cell membrane penetration and reversible thiolation by a cysteine residue of hTRPA1, supported by data from nuclear magnetic resonance experiments with a model thiol, explains the structure-activity relationships. The corre

SUBMITTER: Lindsay CD 

PROVIDER: S-EPMC4448789 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature