AP-18 is a potent and selective TRPA1 inhibitor. AP-18 inhibits activation of TRPA1 induced by 50 μM Cinnamaldehyde with an IC50 of 3.1 μM and 4.5 μM for human and mouse TRPA1, respectively. AP-18 could reverse complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in mice. AP-18 could attenuate Yo-Pro uptake induced by 30 μM AITC in a concentration-dependent manner (IC50= 10.3 μM).

TRPA1:~3 μM

At concentrations up to 50 μM, AP-18 does not significantly inhibit the activation of TRPV1, TRPV2, TRPV3, TRPV4, or TRPM8. However, it effectively and reversibly inhibits the activation of mouse TRPA1 by iodoacetamide (an irreversible cysteine-alkylating agent) in CHO cells, as determined through ratiometric Ca2+ imaging. Additionally, AP-18 prevents cold- and mustard-oil-triggered activation of mouse TRPA1 and inhibits TRPA1 currents induced by cinnamaldehyde in Xenopus oocyte excised patches, demonstrating its specificity and effectiveness in modulating TRPA1 activity [1] [2] [3].

AP18 (1 mM; injected in the hindpaw of mice) effectively inhibits nociceptive events triggered by cinnamaldehyde, but not those induced by capsaicin, demonstrating its specificity and efficacy [1].