ONO-2952 is more selective for TSPO than other receptors, transporters, ion channels, and enzymes. ONO-2952 is a potent and selective translocator protein 18 kDa (TSPO) antagonist (Ki: 0.33-9.30 nM for rat and human TSPO). ONO-2952 has the potential for irritable bowel syndrome treatment. ONO-2952 exerts its anti-stress effects through inhibition of excessive activation of the noradrenergic system in the brain without the amnesic effect.

TSPO (rat and human):（ki）0.33-9.30 nM

ONO-2952 at a concentration of 10 μM displayed good selectivity for TSPO against 98 off-targets (<50% inhibition). ONO-2952 Ki value for the GABAA receptor is more than 600 times higher than that for TSPO. Determination of ONO-2952 Ki or IC50 values for the remaining 35 targets (50% inhibition at 10 μM) reveals Ki values of less than 1 μM only for 3 receptors, i.e. melatonin 2, progesterone B, and adrenergic α2C. The affinity of ONO-2952 for these receptors is at least 59 times lower than that for TSPO [1].

ONO-2952 inhibits both neurosteroid accumulation and noradrenaline release in the brain of rats exposed to acute stress. ONO-2952 also inhibits conditioned fear stress-induced freezing behavior in rats. ONO-2952 (0.03-3 mg/kg; p.o.; male Sprague Dawley rats) treatment dose-dependently inhibits restraint stress-induced defecation in rats with brain TSPO occupancy of more than 50% [1].