Ipamorelin, the first selective growth hormone secretagogue

Area of Science:

• Endocrinology
• Pharmacology
• Peptide Chemistry

Background:

• Growth hormone (GH) secretagogues (GHSs) are compounds that stimulate GH release.
• Existing GHSs, such as growth hormone-releasing peptide (GHRP)-6 and GHRP-2, exhibit varying potencies and efficacies.
• There is a need for GHSs with improved specificity for GH release.

Purpose of the Study:

• To describe the development and pharmacology of ipamorelin, a novel potent GH secretagogue.
• To evaluate the potency, efficacy, and specificity of ipamorelin in vitro and in vivo.
• To compare ipamorelin's pharmacological profile with existing GHRPs and growth hormone-releasing hormone (GHRH).

Main Methods:

• Ipamorelin, a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), was synthesized.
• In vitro studies used primary rat pituitary cells to assess GH release.
• In vivo studies involved pentobarbital-anesthetized rats and conscious swine to measure GH, ACTH, cortisol, FSH, LH, PRL, and TSH levels.

Main Results:

• Ipamorelin demonstrated high GH releasing potency and efficacy in vitro, comparable to GHRP-6.
• In vivo, ipamorelin showed comparable potency and efficacy to GHRP-6 in rats and swine.
• Ipamorelin selectively stimulated GH release without significantly affecting ACTH or cortisol levels, even at high doses, unlike GHRP-6 and GHRP-2.

Conclusions:

• Ipamorelin is a potent GH secretagogue acting through a GHRP-like receptor.
• Ipamorelin exhibits a unique selectivity for GH release, similar to GHRH, without stimulating ACTH or cortisol.
• The specific pharmacological profile of ipamorelin positions it as a promising candidate for future clinical development.