No abstract

It is generally accepted that the orexin 2 receptor (OX 2 R) plays a critical role in the arousal-promoting function, and in vivo imaging of OX 2 R is expected to contribute to elucidation of orexin systems and the development of drugs to treat sleep disorder. In this study, we newly synthesized and characterized a radioiodinated triazole-pyrolidine derivative ([ 125 I]TPI) to detect OX 2 R in the brain. In vitro studies using OX 1 R or OX 2 R expression cells showed selective binding of [ 125 I]TPI to OX 2 R. In addition, in vitro autoradiography using rat brain sections showed high accumulation of radioactivity in the OX 2 R expression region. However, [ 125 I]TPI showed low brain uptake in normal mice. These results suggest that [ 125 I]TPI has a fundamental character to detect OX 2 R in vitro, but further structural modification to improve brain pharmacokinetics is required to use it for in vivo detection of OX 2 R.