Patchett A A, Nargund R P, Tata J R, Chen M H, Barakat K J, Johnston D B, Cheng K, Chan W W, Butler B, Hickey G
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7001-5. doi: 10.1073/pnas.92.15.7001.
A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.
一种强效的口服活性生长激素（GH）促分泌素L-163,191已被鉴定，它属于最近合成的一类结构。L-163,191能从培养的大鼠垂体细胞中释放GH，其半数有效浓度（EC50）为1.3±0.09 nM，在作用机制上与生长激素释放肽GHRP-6和典型的非肽类GH促分泌素L-692,429无法区分，但与天然GH促分泌素生长激素释放激素明显不同。口服低至0.125 mg/kg剂量的L-163,191后，犬体内的GH水平会升高，并且在口服1 mg/kg后，它对GH的释放具有特异性，对血浆醛固酮、促黄体生成素、甲状腺素和催乳素水平无显著影响。仅观察到皮质醇有适度增加。基于这些特性，L-163,191已被选用于临床研究。
