Ipamorelin, the first selective growth hormone secretagogue.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro cell culture and animal model investigation.
PubMed 9849822 · doi:10.1530/eje.0.1390552
What was done
Researchers characterized the pharmacology and selectivity of the pentapeptide ipamorelin in vitro using primary rat pituitary cells and in vivo using pentobarbital-anesthetized rats and conscious swine. They measured growth hormone release potency and efficacy alongside receptor mechanism profiles using growth hormone-releasing peptide and growth hormone-releasing hormone antagonists. In swine, they evaluated endocrine selectivity by measuring plasma concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, adrenocorticotropic hormone, and cortisol compared against GHRP-6 and GHRP-2.
What was found
In rat pituitary cells, ipamorelin stimulated growth hormone release with an EC50 of 1.3 +/- 0.4 nmol/l and Emax of 85 +/- 5%, compared to 2.2 +/- 0.3 nmol/l and 100% for GHRP-6. In anesthetized rats, ipamorelin had an ED50 of 80 +/- 42 nmol/kg and Emax of 1545 +/- 250 ng GH/ml versus 115 +/- 36 nmol/kg and 1167 +/- 120 ng GH/ml for GHRP-6. In conscious swine, ipamorelin had an ED50 of 2.3 +/- 0.03 nmol/kg and Emax of 65 +/- 0.2 ng GH/ml plasma, comparable to GHRP-6 (ED50 3.9 +/- 1.4 nmol/kg, Emax 74 +/- 7 ng GH/ml). In swine, ipamorelin did not alter follicle-stimulating hormone, luteinizing hormone, prolactin, or thyroid-stimulating hormone, and unlike GHRP-6 and GHRP-2, did not significantly elevate adrenocorticotropic hormone or cortisol even at doses exceeding 200-fold its growth hormone ED50.
Why it matters
This study introduces ipamorelin as a potent growth hormone secretagogue receptor agonist that avoids off-target stimulation of ACTH and cortisol seen with earlier peptidomimetics.
Limits
The study is entirely preclinical, testing only in vitro rat cells, anesthetized rats, and swine. Total animal sample sizes, confidence intervals, and long-term tolerability or human pharmacokinetic data are not reported in the abstract.
Cited by
- supports CJC-1295 is a growth hormone-releasing hormone derivative and Ipamorelin is a ghrelin receptor agonist that synergistically stimulate growth hormone release.