ONO-2952 is a potent, selective and orally active translocator protein 18 kDa (TSPO) antagonist with K i of 0.33-9.30 nM for rat and human TSPO . ONO-2952 is more selective for TSPO than other receptors, transporters, ion channels and enzymes. ONO-2952 exerts its anti-stress effects through inhibition of excessive activation of noradrenergic system in the brain without the amnesic effect. ONO-2952 has the potential for irritable bowel syndrome treatment
In Vitro
As for its selectivity for TSPO, ONO-2952 at a concentration of 10 μM showed good selectivity for TSPO against 98 off-targets (<50% inhibition). Determination of ONO-2952 K i or IC 50 values for the remaining 35 targets (50% inhibition at 10 μM) reveal K i 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. ONO-2952 K i value for the GABA A receptor is more than 600 times higher than that for TSPO. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ONO-2952 (0.03-3 mg/kg; oral administration; male Sprague Dawley rats) treatment dose-dependently suppresses restraint stress-induced defecation in rats with brain TSPO occupancy of more than 50%. ONO-2952 also suppresses conditioned fear stress-induced freezing behavior in rats . ONO-2952 inhibits both neurosteroid accumulation and noradrenaline release in the brain of rats exposed to acute stress . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Sprague Dawley rats (8 weeks old) under conditioned fear stress test Dosage: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg Administration: Oral administration Result: Dose-dependently suppressed restraint stress-induced defecation in rats. And suppressed conditioned fear stress-induced freezing behavior in rats.
Form:Solid
IC50& Target:Ki: 0.33-9.30 nM (Rat and human TSPO)
