@ARTICLE{10.3389/fendo.2012.00120, AUTHOR={Thirunarayanan, Nanthakumar and Raaka, Bruce and Gershengorn, Marvin}, TITLE={Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor}, JOURNAL={Frontiers in Endocrinology}, VOLUME={3}, YEAR={2012}, URL={https://www.frontiersin.org/articles/10.3389/fendo.2012.00120}, DOI={10.3389/fendo.2012.00120}, ISSN={1664-2392}, ABSTRACT={Taltirelin (TAL) is a thyrotropin-releasing hormone (TRH) analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R) in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating central nervous system effects in humans compared to TRH.} }