Effect of the Long-Acting Somatostatin Analogue SMS 201–995 on Small-Intestinal Interdigestive Motility in the Dog

Abstract

The long-acting somatostatin analogue SMS 201–995, also called Sandostatin®, is used in the treatment of acromegaly and peptide-secreting tumors. Little is known about its effect on gut motility, although such an effect might be expected considering the spectrum of activities of its parent molecule, somatostatin. We have studied the effect on the interdigestive motility of intravenous boluses of 0, 0.1, 0.5. 1.5, and 5.0 μg/kg of this analogue in 10 dogs with bipolar electrodes implanted along the entire small bowel. All doses induced, within 5 min of administration, premature phase-3 activity that was isolated to one segment, normally progressive, or simultaneous (stationary) in all channels. Only low doses induced isolated phase 3, whereas the frequency of the induction of stationary phase 3 increased with higher doses. In the next cycle of the migrating motor complex the duration of phase 1 was increased, although the duration of the whole cycle was not changed. This cycle ended with mostly ectopic phase-3 activity. During phase 2 of the following cycle ultra-rapid rushes of spiking activity progressing at a speed of 25 ± 3 cm/sec in the upper jejunum were regularly observed. Although this pattern occurs very rarely under control conditions, it was present in 20%, 80%, and 100% of the experiments after doses of 0.5, 1.5, and 5.0 μg/kg, respectively. We conclude that gastrointestinal side effects observed during administration of SMS 201–995 might be related to these motility effects, which warrant further investigation. SMS 201–995 may be a tool to study the mechanism of the induction of ultra-rapid rushes and of stationary phase 3.

Key Words:

• Interdigestive motility
• migrating motor complex
• Sandostatin®
• somatostatin