| Description |
A-967079 is a selective TRPA1 receptor antagonist with IC50s of 67 nM and 289 nM at human and rat TRPA1 receptors, respectively, and has good penetration into the CNS.
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| Related Catalog |
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| Target |
IC50: 67 nM (human TRPA1 receptor), 289 nM (rat TRPA1 receptor)[1]
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| In Vivo |
Systemic injection of A-967079 (30 μmol/kg, i.v.) decreases the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similar to its actions in uninjured rats, administration of A-967079 (30 μmol/kg, i.v.) to complete Freund's adjuvant (CFA)-inflamed rats significantly reduces WDR neuronal responses to noxious pinch stimulation compared to baseline firing (p=0.0013, repeated-measures ANOVA) and the vehicle group (p=0.0001, two-way ANOVA). The maximum observed effect (61.1±10.97% decrease from baseline levels) on pinch-evoked activity in inflamed rats occur 35 min after injection. In contrast to uninjured rats, injection of A-967079 to CFA-inflamed rats also significantly (p=0.0004, and p=0.0001 for the repeated-measures and two-way ANOVA's, respectively) reduces responses of WDR neurons to 10-g von Frey hair stimulation. The maximal observed decrease in von Frey-evoked activity is 67.69±18.39% from baseline levels (35 min post-injection), and is thus comparable to the effects of A-967079 on pinch-evoked activity in inflamed rats[1].
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| Animal Admin |
Rats[1] Male Sprague-Dawley rats (250-400 g) are used for all experiments and are housed in a temperature controlled room with a 12/12-hr day/night cycle. Food and water are available ad libitum. Spontaneous and evoked neuronal activity is then measured 5, 15, 25, and 35 min after systemic injection of A-967079 (30 μmol/kg, i.v.) or vehicle (polyethylene glycol). The intravenous injection of A-967079 or vehicle is completed over a 6-7 min period. The i.v. dose of A-967079 is selected based on extrapolated plasma levels that are effective in behavioral studies[1].
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| References |
[1]. McGaraughty S, et al. TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Mol Pain. 2010 Mar 5;6:14.
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