DESIGN AND BIOLOGICAL-ACTIVITIES OF L-163,191 (MK-0677) - A POTENT, ORALLY-ACTIVE GROWTH-HORMONE SECRETAGOGUE

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 EC(50) = 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.