Comparison of Somatuline (BIM‐23014) and somatostatin on endocrine and exocrine activities in the rat

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Abstract
The actions of Somatuline (BIM‐23014), an Octapeptide analogue of somatostatin, and somatostatin have been compared on several endocrine and exocrine activities in the rat. A substantial difference exists between these two compounds with respect to potency, duration of action, and tissue‐selectivity. With regard to endocrine activities, Somatuline was about 300 times more potent than somatostatin in inhibiting growth hormone (GH) release 15 min after intravenous injection, and about 4 to 6 times more potent 15 min after subcutaneous administration. The inhibitory activity of subcutaneously‐administered Somatuline on D‐ALa2‐GRF‐stimulated GH release lasted for about 6 hr, whereas an action of somatostatin was not detected 30 min after injection. Somatuline was also more potent than somatostatin in inhibiting insulin‐stimulated glucagon secretion when both substances were administered intravenously, whereas they were about equipotent when given by the subcutaneous route. However, Somatuline was only about half as potent as somatostatin by the intravenous route in inhibiting glucose‐stimulated insulin release and inactive by the subcutaneous route. With regard to exocrine activities, Somatuline was about 300–500 times more potent than somatostatin in inhibiting the increase in plasma α‐amylase activity following ligation‐induced pancreatitis when both compounds were administered subcutaneously concurrently with pancreatic duct ligation. Somatuline was also about 20–400 times more potent that somatostatin in inhibiting gastric acid secretion when both compounds were administered subcutaneously prior to, or concurrently with, pentagastrin challenge, and about 100 times more potent than somatostatin when administered after pentagastrin challenge. Somatuline had a very weak inhibitory effect on the development of ethanol induced gastric ulcers, it did not induced diarrhea, and it had no effect on the course of diarrhea in rats subjected to castor oil gavage. The differences that have been shown to exist between Somatuline and somatostatin indicate that Somatuline may be more useful in treating certain disease states, such as diabetes mellitus, pancreatitis, and possible gastritis or bleeding gastric ulcers.