HEXARELIN(TM) [HIS-D-2METHYL-TRP-ALA-TRP-D-PHE-LYS-NH2], A NEW GH-RELEASING PEPTIDE, IS BIOLOGICALLY-ACTIVE IN MALE AND FEMALE RATS

The present study was conducted in order to evaluate the CH-releasing bioactivity of intravenously (iv), subcutaneously (sc), and orally (po) administered His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 [Hexarelin(tm)] in male and female rats. Animals were administered Hexarelin(tm) parenterally iv or sc, and enterally by gastrogavage (po). Blood was collected before and after peptide administration for comparison of the plasma GH response for each of the three different modes of administration. An iv dose of 1 mu g/kg appeared to approach the minimum effective dose, while the maximum effective iv dose may lie between 100 and 400 mu g/kg. The peak-response was found to occur at 7 +/- 1 min post-treatment. As seen with iv administration, sc Hexarelin(tm) elicited plasma CH responses in a dose-dependent fashion. Due to the limited range of doses studied, the minimum effective dose was not determined. The peak plasma CH response following sc Hexarelin(tm) occurred at 13 +/- 2 min. Oral Hexarelin(tm) was less potent than when given either iv or sc, but was still able to elicit significant plasma GH responses in a general dose-dependent fashion between 100 and 1000 mu g/kg. The average time of peak CH response following po Hexarelin(tm) (80 +/- 11 min) occurred later than that noted for either iv or sc Hexarelin(tm). These results demonstrate that Hexarelin(tm) is biologically active when administered iv, sc or po. Hexarelin(tm) may prove to be a significant new member of the growth hormone-releasing peptides class of CH-releasing molecules.