• DOI:10.1385/ENDO:14:1:121
• Corpus ID: 46978604

Preclinical pharmacology of CP-424,391, and orally active pyrazolinone-piperidine growth hormone secretagogue

@article{Pan2007PreclinicalPO,
  title={Preclinical pharmacology of CP-424,391, and orally active pyrazolinone-piperidine growth hormone secretagogue},
  author={Lydia C. Pan and Philip Albert Groton Carpino and Bruce A. Lefker and John A. Ragan and Steven M. Toler and John C. Pettersen and David O. Nettleton and Oicheng Ng and Christine M. Pirie and Kristin L Chidsey-Frink and Bihong Lu and David F. Nickerson and David A. Tess and Michelle A Mullins and David B. Maclean and Paul A DaSilva-Jardine and David Duane Thompson},
  journal={Endocrine},
  year={2007},
  volume={14},
  pages={121-132}
}

• L. Pan, P. Carpino, +14 authors D. Thompson
• Published 1 February 2001
• Biology, Medicine
• Endocrine

Growth hormone secretagogues (GHSs) represent attractive therapeutic alternatives to recombinant growth hormone (GH), given their ability to amplify pulsatile hormone secretion in a relatively physiologic manner. CP-424,391 (391) is a novel, orally active pyrazolinone-piperidine GHS. In rat pituitary cell cultures, 391 stimulated GH release with an EC50=3 nM. The addition of 391 to rat pituitary cells activated intracellular calcium signaling but did not elevate intracellular cyclic adenosine monophosphate (cAMP). 391 also modulated the effects of GH-releasing hormone and somatostatin on pituitary cell GH-release and intracellular signaling. In nonpituitary cell lines, the ability of 391 to stimulate intracellular signaling was dependent on the expression of recombinant human GHS receptor. Acute administration of 391 to anesthetized rats or to conscious dogs induced pulsatile release of GH in a dose-dependent manner. Plasma insulin-like growth factor-1 (IGF-1) was elevated progressively over a 5-d course of daily oral dosing in dogs. Chronic oral administration of 391 augmented body weight gain in rats and dogs. Thus, the peptidomimetic GHS 391 has potential utility for the treatment of clinical conditions that could benefit from systemic augmentation of GH and IGF-1 levels.