AM-0902 is a potent and specific TRPA1 antagonist (IC50s: 71/131 nM for rTRPA1 and hTRPA1).

TRPA1 (human):131 nM, TRPA1 (rat):71 nM

AM-0902具有很高的渗透性（MDCK细胞中平均Papp=44.5 μcm/s），不太可能是P-gp的底物（在过表达P-gp的MDCK细胞中，efflux ratio=1.3），并且展现出良好的溶解性（PBS pH 7.4：226 μM，SIF：248 μM）。AM-0902对其他TRP通道具有良好的选择性，因为在高达10 μM的浓度下，未观察到针对人类的TRPV1或TRPV4，或大鼠的TRPV1、TRPV3、TRPM8的活性。AM-0902在甲基乙二醛激活的大鼠TRPA1上抑制45Ca2+通量（IC50：0.019 μM）。

AM-0902表现出中等的终末消除半衰期（t1/2=0.6 h和2.8 h，分别对于大鼠（0.5 mg/kg, iv）和大鼠（30 mg/kg, oral））。对于AM-0902，观察到剂量依赖性地减少了丙烯基异硫氰酸酯(AITC)-引起的缩足反应，特别在给药后的10 mg/kg和30 mg/kg剂量，显著减少了缩足反应。1小时内未结合的血浆浓度（Cu）对于1, 3, 10, 以及30 mg/kg的剂量分别为0.051±0.024, 0.19±0.11, 0.58±0.35, 和2.2±0.40 μM，相对于体外大鼠TRPA1 45Ca2+ IC50的倍数分别为0.72, 2.7, 8.2, 和30.3倍。在此靶点覆盖模型中，观察到良好的曝光-反应关系。确定了未结合的体内IC50为0.35 μM，与体外大鼠TRPA1 45Ca2+ IC50高度一致，并且未结合的体内IC90为1.7 μM。值得注意的是，在30 mg/kg的剂量下，AM-0902以超过体内IC90的浓度作用于TRPA1，使其成为探索急性痛模型的有用工具。

On the day of assay, culture media is removed and MDCK cells are incubated for 10 min at room temperature (RT) with 50 μL of AM-0902 in AM-0902 dilution buffer [HBSS containing 1 mM HEPES+0.1 mg/mL BSA] at final concentrations (2.0 nM to 40 μM, 1:3 ratio), followed by another 3 min incubation at RT. The reaction mixture is aspirated, and cells are washed three times with PBS containing 0.1 mg/mL BSA. Radioactivity is measured using a TopCount microplate scintillation counter. The activation of TRPA1 is measured by the cellular uptake of radioactive calcium.

Rats are dosed orally with either vehicle (2% HPMC/1% Tween-80) or AM-0902 at 1, 3, 10, or 30 mg/kg. After 1 h, one left ventral hind paw is injected with the TRPA1 agonist AITC (0.1%). AM-0902 is also given by an intravenous (IV) injection to rats (0.5 mg/kg).