A-967079

Использование

(1E,3E)- 1-(4-Fluorophenyl)-2-methyl-1-penten-3-one Oxime is a transient receptor potential ankyrin 1 (TRPA1) antagonist and has been investigated as potential analgesic drug for the treatment of chronic pain.

Общее описание

A-967079 prevents neuropathic and inflammatory pain. It reduces cold allodynia, which is produced by nerve injury.

Биохимия/физиол Действия

A-967079 is a potent and selective antagonist of Transient Receptor Potential Anykrin 1 (TRPA1) with IC50′s of 67 nM and 289 nM at human and rat TRPA1 receptors, respectively, and minimal or no activity at other TRP channels or G-protein-coupled receptors, enzymes, transporters, and ion channels out of 89 tested. A-967079 blocks TRPA1 activation in human and rat cell lines and has been shown to reduce the responses of wide dynamic range (WDR) and nociceptive specific (NS) neurons to high-intensity mechanical stimulation.

преимущество

(1E,3E)-1-(4-Fluorophenyl)-2-methyl-1-pentene-3-one oxime (A-967079) has shown impressive efficacy as an antagonist to TRPA1 and has multiple advantages over other compounds, including high selectivity, potency, and oral bioavailability. A-967079 has IC50 values of 67 and 289 nM for human and rat TRPA1 receptors, respectively. It displays 1000-fold selectivity for TRPA1 over other TRP channels, and >150-fold selectivity for over 75 other ion channels, enzymes and G-protein-coupled receptors. Oral administration of A-967079 in rats produced robust bioavailability and analgesic efficacy for TIH-induced pain response (i.e., sneezing, tearing, coughing, etc.) and osteoarthritic pain. Intravenous injection of A-967079 has shown to decrease the reactive gas response of wide dynamic range neurons (i.e., a second-order neuron that responds to more than one type of stimulus) and pain specific-neurons. Aditionally, A-967079 produces no known locomotor or cardiovascular effects, a common side effect of other TRP antagonists[2].