Deghenghi R
Europeptides, Argenteuil, France.
Acta Paediatr Suppl. 1997 Nov;423:85-7. doi: 10.1111/j.1651-2227.1997.tb18381.x.
The discovery and development of growth hormone (GH) secretagogues is briefly reviewed. GH-releasing peptide-6 (GHRP-6) was the first GHRP to be developed that was active in vivo. Smaller peptides were found to have no GH-releasing activity in vivo, even though they were potent releasers of GH in vitro. Substituting Trp with 2-Me-Trp led to the development of orally active hexarelin and other, smaller, peptides. Although they showed oral activity, absorption rarely exceeded 1% of the administered dose. Nonpeptide GH secretagogues have now been developed that combine reasonable oral absorption with high potency. The next development will be to produce GH secretagogues that overcome the lack of specificity shown by the present molecules.
本文简要回顾了生长激素（GH）促分泌素的发现与发展历程。生长激素释放肽-6（GHRP-6）是首个在体内具有活性的生长激素释放肽。尽管较小的肽在体外是有效的生长激素释放剂，但发现它们在体内没有生长激素释放活性。用2-甲基色氨酸替代色氨酸促使了口服活性六肽生长激素释放肽及其他更小的肽的研发。尽管它们具有口服活性，但其吸收量很少超过给药剂量的1%。目前已研发出非肽类生长激素促分泌素，这类物质兼具合理的口服吸收性与高效性。下一步的发展方向将是研发出能克服当前分子所表现出的特异性不足问题的生长激素促分泌素。
