Anti-stress effects of ONO-2952, a novel translocator protein 18k | 48792

Journal of Neuroscience and Neuropharmacology

Anti-stress effects of ONO-2952, a novel translocator protein 18kDa (TSPO) antagonist

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Takashi Kitajima

ONO Pharmaceutical Co., Ltd., Japan

Scientific Tracks Abstracts: Neurochem Neuropharm

Abstract :

The translocator protein 18kDa, TSPO is mainly located in the outer mitochondrial membrane of steroid producing cells, including glial cells, and regulates cholesterol transport from intracellular sources into mitochondria, a rate-limiting step in steroidogenesis. Neurosteroids act as allosteric modulators of excitatory and/or inhibitory neurotransmission and its levels are drastically changed by stress. ONO-2952, a novel selective TSPO antagonist inhibited both stress-induced increase in neurosteroid production and noradrenaline release in the brain of stressed rats. ONO-2952 dose-dependently inhibited stressinduced rectal hyperalgesia and defecation with brain TSPO occupancy of more than 50%. In addition, ONO-2952 inhibited conditioned fear stress-induced freezing behavior and cholecystokinin tetrapeptide, CCK-4 induced anxiety behavior with an efficacy equivalent to that of benzodiazepines. It should be noted that ONO-2952, unlike diazepam, did not affect passive avoidance behavior. Furthermore, ONO-2952 inhibited hyperemotionality and anxiogenic-like behavior in olfactory bulbectomized rat. In fibromyalgia models, ONO-2952 inhibited hyperalgesia induced by repeated cold stress or acid saline injection. The present findings indicate that ONO-2952 is a promising candidate for the treatment of stress-related disorders, such as irritable bowel syndrome, depression, anxiety disorders and fibromyalgia.

Biography :

Takashi Kitajima joined ONO Pharmaceutical Co., Ltd. after graduating from University of Shizuoka in 2000. He is a Research Project Leader of ONO-2952 and a Head of Group II, Discovery Research Laboratories I.