Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptanon interdigestive gastrointestinal motility in man

Background—Pharmacological studies of the entericnervous system have shown the presence of several subtypes of5-hydroxytryptamine (5HT) receptor, which might be involved incontrol of the migrating motor complex.
Aims—To study the effect of sumatriptan, anagonist of enteric neuronal 5HT_1P receptors, oninterdigestive motility in man.
Subjects and methods—In 12 healthy subjects,interdigestive motility was recorded manometrically in the uppergastrointestinal tract. In seven subjects blood samples were drawnevery 15 minutes for radioimmunoassay of motilin and somatostatin.After two phase 3s of the migrating motor complex, 6 mg of sumatriptanwas administered subcutaneously. Recording continued until two morephase 3s had occurred.
Results—Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of themigrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilinconcentrations and the occurrence of plasma motilin peaks were notaffected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented theinduction of a gastric phase 3 by the motilin agonist erythromycin.
Conclusions—Administration of the5HT_1P receptor agonist sumatriptan induces a prematureintestinal phase 3, suppresses gastric phase 3s, prevents induct-ion of a gastric phase 3 by erythromycin, and reduces plasmasomatostatin concentrations.

Keywords:migrating motor complex; motilin; somatostatin; erythromycin; enteric nervous system