Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue
| Autor: | Kang Cheng, M H Chen, K J Barakat, G. J. Hickey, D B Johnston, Arthur A. Patchett, Ravi P. Nargund, Wanda W.-S. Chan, J R Tata, B Butler |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Indoles Molecular Sequence Data Administration Oral Tetrazoles Peptide Pharmacology Biology chemistry.chemical_compound Structure-Activity Relationship Dogs Oral administration Growth hormone secretagogue Internal medicine medicine Animals Spiro Compounds Amino Acid Sequence Aldosterone Cells Cultured chemistry.chemical_classification Multidisciplinary Drug Synergism Benzazepines Luteinizing Hormone Prolactin Rats Thyroxine Endocrinology chemistry Drug Design Growth Hormone Pituitary Gland Injections Intravenous Secretagogue Luteinizing hormone Oligopeptides Hormone Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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