A-967079

A-967079 is a selective TRPA1 receptor antagonist with IC₅₀s of 67 nM and 289 nM at human and rat TRPA1 receptors, respectively, and has good penetration into the blood-brain barrier^[1]. IC50 & Target:IC50: 67 nM (human TRPA1 receptor), 289 nM (rat TRPA1 receptor)^[1] In Vivo:Systemic injection of A-967079 (30 μmol/kg, i.v.) decreases the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similar to its actions in uninjured rats, administration of A-967079 (30 μmol/kg, i.v.) to complete Freund's adjuvant (CFA)-inflamed rats significantly reduces WDR neuronal responses to noxious pinch stimulation compared to baseline firing (p=0.0013, repeated-measures ANOVA) and the vehicle group (p=0.0001, two-way ANOVA). The maximum observed effect (61.1±10.97% decrease from baseline levels) on pinch-evoked activity in inflamed rats occur 35 min after injection. In contrast to uninjured rats, injection of A-967079 to CFA-inflamed rats also significantly (p=0.0004, and p=0.0001 for the repeated-measures and two-way ANOVA's, respectively) reduces responses of WDR neurons to 10-g von Frey hair stimulation. The maximal observed decrease in von Frey-evoked activity is 67.69±18.39% from baseline levels (35 min post-injection), and is thus comparable to the effects of A-967079 on pinch-evoked activity in inflamed rats^[1].