ASIC blocker (IC50 values are 0.44, 2.1 μM and no effect at rat ASIC1a, ASIC3 and ASIC2a, respectively: IC50 value = 0.12 μM at human ASIC1a with no effect at ASIC2a or ASIC3). Inhibition was also observed at heteromeric ASIC channels (IC50 values are 0.79, 0.87 and 4.5 uM at rat ASIC1a+3, ASIC1a+2a and ASIC2a+3; IC5O values are 0.33 and 0.69 uM at human ASIC1a+2a and ASIC1a+3, with no effect at ASIC2a+3). Attenuates pathophysiological nociceptive behaviors in CFA-inflamed and CCI rats.
CAY10680 is a dopamine-sparing, benzothiazinone compound that selectively inhibits both MAO-B activity (IC50 = 34.9 nM in human) and adenosine A2A receptors (Ki = 39.5 nM in human). It demonstrates significantly less potent inhibitory values for other adenosine receptor subtypes (Kis > 1 μM) and MAO-A (IC50 ≥ 10 μM). At 1-20 μM, CAY10680 has been shown to abolish cAMP accumulation in CHO cells transfected with adenosine A2A receptors. In the central nervous system adenosine A2A receptor expression is localized to dopamine-innervated areas where heteromeric complexes are formed with dopamine D2 receptors. Because inhibition of adenosine A2A receptors has been shown to enhance D2 receptor function, the blockade of adenosine A2A receptors has emerged as a potential treatment for Parkinson's disease. An additional strategy in the treatment of Parkinson's disease has been to block the activity of monoamine oxidase B (MAO-B), the enzyme involved in dopamine catabolism.