In vitro activity: Emapunil (formerly known as AC-5216 or XBD-173) is an antianxiolytic drug that also has neuroprotective activities. It acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO. TSPO is a five transmembrane domain protein (18 kDa) that is expressed predominantly in steroid-synthesizing tissues. This protein has multiple functions including the regulation of steroidogenesis, in particular the production of neuroactive steroids such as allopregnanolone in the brain. Emapunil exerts anxiolytic effects not only in animal models, but also in human volunteers. As a ligand for TSPO, AC-5216 produces anxiolytic- and antidepressant-like effects in animal models. The antidepressant-like effects of AC-5216 on HFD-STZ rats, suggests that TSPO may represent a novel therapeutic target for depression in T2DM.

Kinase Assay: TSPO ligand XBD173 enhanced gamma-aminobutyric acid-mediated neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation or withdrawal symptoms

Cell Assay:

XBD173 was synthesized by our chemist partners (F. Hallé and F. Bihel) according to the experimental procedure reported by Zhang et al. The mice received i.p. injections (200 μl) of XBD173 at a dose of 10, 20 or 30 mg/kg (n = 26 for the groups 10 and 20 mg/kg, at the beginning of the experiments and n = 8 for the group 30 mg/kg), depending on the body weight, dissolved in hydroxypropyl cellulose (HPC) 0.3% (Alfa Aesar, Haverhill, Massachusetts, USA) and vehicle mice were injected with HPC 0.3% (n = 23, at the beginning of the experiments) according to a similar schedule. Mice were treated every two days from D4 until sacrifice.