L-692,585 produced 4-7 fold GH increases in dogs with maintained efficacy over 15 days of daily dosing and significantly elevated IGF-1 by day 15.
15 days, no toleranceDaily L-692,585 dosing maintained GH release and raised IGF-1 — no desensitization over 15 days
What the researchers found
L-692,585 produced 4.3 to 7-fold increases in peak GH with maintained efficacy over 15 days of daily dosing and elevated IGF-1 by day 15.
Why it matters
Non-peptide GH secretagogues can be taken by mouth, unlike peptide versions that need injection. This study showed L-692,585 maintains its effect with repeated dosing, a key requirement for practical clinical use.
How the study worked
Eight beagle dogs received single IV doses of L-692,585 at three dose levels or saline in a balanced study. A separate group received daily doses for 15 days with GH, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine measured.
What this study cannot tell us
Animal study in dogs. Beagle GH physiology differs from humans. Only 15 days of repeated dosing was tested. Intravenous route used rather than oral.
How to read the evidence
Moderate — animal study in dogs with repeated-dose design. 8-dog balanced study with multiple endpoints.
When this study was published
Published in 1994 (32 years ago). This work contributed to MK-677 development, which has longer-term human data.
The bigger picture
For a GH secretagogue to work clinically, it must not lose effectiveness with repeated dosing. This study proved that a non-peptide GH-releasing drug can sustain its effects over time — a crucial milestone toward drugs like MK-677.
Questions still open
- Does efficacy persist beyond 15 days?
- Would oral bioavailability allow practical human use?
Common questions
Why does maintaining effectiveness matter?
What is IGF-1 and why did it rise?
Read the original research
Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles.
The Journal of endocrinology, 143(2), 399-406
Citation
Jacks, T; Hickey, G; Judith, F; Taylor, J; Chen, H; Krupa, D; Feeney, W; Schoen, W; Ok, D; Fisher, M. (1994). Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles.. The Journal of endocrinology, 143(2), 399-406.