although several nonelectrophilic agents such as thymol and menthol have been reported as trpa1 agonists, most of the known activators are electrophilic chemicals that have been shown to activate the trpa1 receptor via the formation of a reversible covalent bond with cysteine residues present in the ion channel. for a broad range of electrophilic agents, chemical reactivity in combination with a lipophilicity enabling membrane permeation is crucial to trpa1 agonistic effect. a dibenz["b,f"][1,4]oxazepine derivative substituted by a carboxylic methylester at position 10 is the most potent trpa1 agonist discovered to date (ec = 50 pm). the pyrimidine pf-4840154 is a potent, non-covalent activator of both the human (ec = 23 nm) and rat (ec = 97 nm) trpa1 channels. this compound elicits nociception in a mouse model through trpa1 activation. furthermore, pf-4840154 is superior to allyl isothiocyanate, the pungent component of mustard oil, for screening purposes.