生物活性

• 描述TRPA1, a nonselective cation channel and member of the transient receptor potential (TRP) superfamily of ion channels, is highly expressed in sensory neurons of the dorsal root ganglia and is activated by a range of irritants. AM-0902 is a potent and selective TRPA1 antagonist with IC50 values of 0.02μM and 0.024μM for hTRPA1 and rTRPA1, respectively. AM-0902 could inhibit Ca²⁺ entering the cell upon activation and opening of the channel with AITC with IC50 value of 0.131μM and 0.071μM for hTRPA1 and rTRPA1, respectively. Oral pre-treatment with AM-0902 at dose of 10mg/kg and 30mg/kg 1h before injection of AITC (0.1%) significantly reduced the AITC flinching in rats. Application of AM-0902 significantly attenuated the elevated frequency of spontaneous EPSCs and miniature EPSCs, the amplitude of monosynaptic EPSCs evoked from the dorsal root in lamina I neurons of CFA-treated rats without effect on evoked or miniature EPSCs in lamina I neurons of vehicle-treated rats. Also, intrathecal injection of AM-0902 significantly reduced pain hypersensitivity in CFA-treated rats without effect on acute nociception in vehicle-treated rats.

• 动物研究
  剂量	Mice: 30 mg/kg[1] (p.o.) Rat: 0.5 mg/kg[2] (i.v.); 30 mg/kg[2] (p.o.), 0.3 mg/kg - 300 mg/kg[3] (p.o.)
  给药途径	p.o., i.v.
  动物药代数据	Animal Rats[2] Dose 0.5 mg/kg (i.v.) 30 mg/kg (p.o.) Administration i.v. p.o. F 60% (p.o.) AUCinf 19.8 μM·h (p.o.) T1/2 0.6 h (i.v.) 2.8 h (p.o.) Tmax 0.8 h (p.o.) CL 2.5 L/h/kg (i.v.) Cmax 7.5 μM (p.o.) CLu 9 (i.v.) Vss 1.7 L/kg (i.v.)