ONO-8590580

Animal experiment:

Rats[1]Male Sprague-Dawley rats are used. ONO-8590580 is orally administered 1 h before sacrifice. [3H]-Ro15-4513 (1.11 MBq/kg) is administered via the tail vein (1 mL/kg) 10 min before sacrifice. Rats (n=12 in each group) are given either vehicle, ONO-8590580 (20 mg/kg, p.o.), or as a positive control, the GABAA nonselective NAM FG-7142 (15 mg/kg, i.p.). After 1 h, rats are placed in the elevated plus maze for 5 min. Light intensity in the open arms is set at 20 lx. A video camera fitted with a polarizing lens is mounted above the maze, connected to a tracking and analyse system[1]. Mice[1]Mice (n=8 in each group) are intraperitoneally administered with either vehicle, ONO-8590580 (10 mg/kg), or FG-7142 (10 mg/kg). After 30 min, the mice are infused with 15 mg/mL PTZ solution (infusion rate 0.2 mL/min), and the time taken to reveal clonic seizures is measured, and from this the dose administrated is calculated[1].

References:

[1]. Kawaharada S, et al. ONO-8590580, a Novel GABAAα5 Negative Allosteric Modulator Enhances Long-Term Potentiation and Improves Cognitive Deficits in Preclinical Models. J Pharmacol Exp Ther. 2018 Jul;366(1):58-65.