Animal only
This animal study investigated whether ghrelin receptor agonists (ghrelin mimetics) could reduce visceral and somatic pain in the absence of active inflammation. Using a rat model, researchers induced non-inflammatory visceral hypersensitivity by infusing dilute acetic acid into the colon, and somatic mechanical allodynia was also assessed. Two ghrelin receptor agonists were tested: HM01, a centrally and peripherally active compound administered orally, and ipamorelin, a peripherally restricted compound administered intravenously. Pain responses were measured by counting abdominal muscle contractions during colorectal distension (visceral pain) and paw withdrawals to von Frey filament stimulation (somatic pain). The study found that both HM01 and ipamorelin significantly reduced colonic hypersensitivity and somatic allodynia compared to vehicle controls. These effects were reversed by co-administration of the ghrelin receptor antagonist H0900, confirming that the anti-nociceptive effects were receptor-mediated. Notably, the peripherally restricted compound ipamorelin was effective, suggesting peripheral ghrelin receptor activation may be sufficient. The study is limited by its exclusive use of an animal model, meaning translational relevance to humans remains unestablished. The authors propose ghrelin mimetics as a potential novel approach for treating acute visceral and somatic pain.
Journal of experimental pharmacology · Aug 2020DOI ↗ Animal only
This study investigated the effects of intra-articular injections of AOD9604 (a synthetic peptide fragment of human growth hormone) alone and in combination with hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model. Thirty-two mature New Zealand white rabbits had OA induced in both knees via collagenase injection, then were divided into four groups receiving weekly intra-articular injections of saline, HA alone, AOD9604 alone, or AOD9604 combined with HA. At eight weeks, outcomes were assessed via gross morphology, histopathology of cartilage, and lameness scoring. The study found that all treatment groups showed significantly less cartilage degeneration than the saline control group. The combination of AOD9604 and HA produced significantly lower cartilage damage scores and shorter lameness periods compared to either treatment alone. While these findings suggest a potential chondroprotective and synergistic effect, the study is limited by its animal-only design, relatively small group sizes, and the use of a chemically induced OA model that may not fully replicate human OA pathology. No human data were collected, so translation of findings to clinical practice remains uncertain.
Annals of clinical and laboratory science · Jan 2015Source ↗ Animal only
This animal study investigated how human growth hormone (hGH) and a synthetic lipolytic fragment derived from its C-terminus, AOD9604, affect fat metabolism and body weight in obese and genetically modified mice. Obese mice received 14 days of chronic intraperitoneal administration of either compound. Both hGH and AOD9604 reduced body weight and body fat in obese mice, and these effects were associated with increased expression of beta-3 adrenergic receptor (β3-AR) RNA — a key receptor involved in fat breakdown — bringing levels in obese mice closer to those seen in lean mice. To test whether β3-AR was essential to these effects, the researchers used β3-AR knock-out mice; in these animals, chronic treatment with either compound failed to produce the body weight reduction or increased lipolysis seen in normal mice. However, in an acute experiment, AOD9604 still increased energy expenditure and fat oxidation in knock-out mice, suggesting additional mechanisms exist. The authors concluded that while neither compound acts directly through β3-AR, both upregulate its expression, which may amplify lipolytic sensitivity over time. Key limitations include the exclusively animal-based design and the use of intraperitoneal administration, limiting direct translation to humans.
Endocrinology · Dec 2001DOI ↗ Animal only
This study compared the pharmacokinetics of five peptidyl growth hormone secretagogues — ipamorelin (NNC 26-0161), NNC 26-0194, NNC 26-0235, GHRP-2, and GHRP-6 — in male rats using multiple routes of administration, with a particular focus on nasal delivery. Following intravenous bolus injection, all peptides showed biexponential plasma concentration decline. Ipamorelin stood out with a systemic plasma clearance approximately five times lower than GHRP-6. Excretion routes differed: ipamorelin was primarily cleared via urine, while GHRP-6 and the two NNC peptides were predominantly excreted in bile. Metabolic stability was moderate for ipamorelin and the NNC peptides, with 60–80% of administered doses recoverable as intact peptide from bile and urine combined. Intranasal bioavailability of ipamorelin was estimated at approximately 20%, while NNC 26-0235, NNC 26-0194, and GHRP-2 achieved approximately 50% nasal bioavailability. The authors concluded that nasal delivery appears to be a promising route for this peptide class. Key limitations include exclusive use of animal subjects (male rats), meaning findings may not directly translate to humans, and the study did not assess pharmacodynamic or safety endpoints.
Xenobiotica; the fate of foreign compounds in biological systems · Nov 1998DOI ↗