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 micrograms/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 micrograms/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.

Octreotide in gastrointestinal motility disorders.

“…Normal subjects showed propagative intestinal patterns during fasting with mean (SD) [1][2][3][4][5] (1 0) phase III complexes occurring every three hours (Fig 1). In contrast, none of the patients with scleroderma with pseudo-obstruction and bacterial overgrowth had any spontaneous duodenal phase III activity (Fig 1).…”

Response to Octreotide of Intestinal Pseudoobstruction and Pneumatosis Cystoides Intestinalis Associated with Progressive Systemic Sclerosis.

“…It might be possible that octreotide directly reduced the production of intestinal gas. However, somatostatin stimulates intestinal motility in normal individuals (16) and octreotide is known to produce a similar effect in dogs (17). Indeed, Soudah et al ( 1 8) confirmed that octreotide increases intestinal motility in patients with progressive systemic sclerosis.…”

Amelioration of intestinal dysmotility and stasis by octreotide early after small-bowel autotransplantation in dogs

“…The type of octreotide-induced phase-3-like contractions was analyzed according to the criteria described by Peeters et al, 16 who defined phase-3-like contractions seen either in jejunal or ileal sites as "isolated" contractions, those propagating from jejunum to ileum as "propagated" contractions, and those observed simultaneously in both the jejunum and the ileum as "simultaneous" contractions. The maximum diameter of the bowel graft was measured in radiographs before and 30 minutes after octreotide injection.…”

“…16 Since the extrinsic nerve has been shown to modulate initiation or propagation, or both, of phase 3 contractions in the small bowel, 25 denervation may have influenced the pattern of phase-3-like contractions in the intestinal grafts.…”

“…After abdominal surgery, disappearance of phase 3 contractions and resulting intestinal stasis have been observed. [12][13][14][15][16][17][18][19] The duration of the disappearance correlated with the severity of operative insults. After intestinal transplantation, reappearance of these contractions was greatly delayed.…”