Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone secretagogue, in beagles.

L-692,429 is a substituted benzolactam that has recently been shown to stimulate GH secretion from rat pituitary cells in vitro with an ED50 of 60 nM. In the current studies, we evaluated the efficacy and specificity of L-692,429 as a GH secretagogue in beagles. L-692,429 at 0.1, 0.25, or 1.0 mg/kg or saline vehicle was administered iv to four male and four female beagles in a balanced cross-over design. Blood samples were collected up to 75 min posttreatment, and serum was assayed for GH, cortisol, PRL, and LH. Mean peak serum GH levels were significantly increased (P < 0.05) by L-692,429 to 13 +/- 2 (mean +/- SEM) ng/ml (0.1 mg/kg), 39 +/- 6 ng/ml (0.25 mg/kg), or 71 +/- 11 ng/ml (1.0 mg/kg) over the saline control value of 3.6 +/- 0.6 ng/ml. Mean peak GH levels occurred at 15 min and had returned to near-baseline levels by 75 min. There was no difference in response between sexes. Mean peak cortisol levels were significantly increased (P < 0.05) by 2.2-, 2.7-, and 3.1-fold above control levels (3.0 +/-...