Transient receptor potential cation channel A1 (TRPA1) is an ankyrin-like ion channel which acts as a sensor for chemical irritants, pain, and cold. It is activated by allyl isothiocyanate (AITC), formalin, hydrogen peroxide, tear gas, and other compounds. HC-030031 is a selective TRPA1 blocker, antagonizing TRPA1-mediated calcium influx induced by AITC and formalin (IC50s = 6.2 and 5.3 μM, respectively). It does not block currents mediated by TRPV1, TRPV3, TRPV4 hERG, or NaV1.2 channels. HC-030031 can be used in cells or delivered to animals orally, by inhalation, or by injection. Oral administration (100 mg/kg) of HC-030031 significantly reversed mechanical hypersensitivity in rat models of chronic inflammatory or neuropathic pain, while local injection (100 μg) into inflamed mouse hind paws attenuated mechanical, but not heat, hypersensitivity.
A TRPA1 (transient receptor potential) selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity.
Selective TRPA1 channel blocker that antagonizes AITC- and formalin-evoked calcium influx (IC 50 values are 6.2 and 5.3 μ M respectively). Does not block currents mediated by TRPV1, TRPV3, TRPV4, hERG or Na V 1.2 channels. Inhibits AITC- and formalin-induced flinching in vivo .
HC-030031 is a selective TRPA1 channel blocker, antagonizing formalin-evoked calcium influx and formalin-induced pain. IC50 is 5 μM. TRPA1 antagonism is a promising therapeutic target for chronic inflammatory or neurogenic pain.
1) McNamara et al. (2007), TRPA1 mediates formalin-induced pain; Proc. Natl. Acad. Sci., 104 13525
