Effects of Domperidone on Human Plasma Levels of Motilin, Somatostatin, Gastrin, Adrenocorticotropic Hormone and Cortisol

Abstract

Domperidone is an antinauseant and gastrokinetic drug which has been reported to be effective for treating functional gastrointestinal disorders such as dyspepsia, gastroesophageal reflux, nausea and vomiting. Domperidone also has recently been evaluated for its clinical usefulness in stress and depression. This medicine has frequently been used in the treatment of chronic hypofunction of the gastrointestinal system. 1,2) Some patients who take this medicine do not have organic diseases such as peptic ulcer, reflex esophagitis, and gastric cancer but have conditions classified as non-ulcer dyspepsia (NUD). Most NUD patients tend toward depressive and psychosomatic conditions and are exposed to continual affective stress.3) This continual stress causes abnormalities in the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous function. 4,5) Some abnormalities of gastrointestinal function are presumed to result from changes in hormone levels. However, the mechanism is not clear.The gastrointestinal peptide motilin is found in specific endocrine cells of the upper small intestine of hogs.6) This peptide strongly stimulates fundic pouch activity 7) and plays an important physiological role in intestinal contractility, particularly in the fundus and antral of the pouch of the stomach. It is one of the most important factors controlling the regular occurrence of phase III interdigestive migrating contractions. 8,9) Somatostatin is present in high amounts in the stomach. 10)This peptide inhibits the secretion of motilin and gastrin, and it also inhibits gastric, duodenal, and biliary motility. 11)Gastrin was first detected in extracts of pyloric antral mucosa.12) The most potent actions of gastrin are the stimulation of both gastric acid secretion and antral motility. 13)Adrenocorticotropic hormone immunoreactive substances (ACTH-IS) are found in tissues other than the pituitary gland (i.e. brain, adrenal gland, gastrointestinal tract, pancreas, thyroid gland, and placenta). The secretion of ACTH is affected by mechanisms of circadian rhythm and negative feedback by blood cortisol, and neurogenic stimulation.14) Plasma levels of ACTH increase under stress and the peptide has the secretomotory action of glucocorticoid. 4) Cortisol, commonly used to indicate the level of stress, is secreted by the zona fasciculate of the adrenal cortex and its secretion is dependent on the ACTH level.In general, venipuncture for blood sampling is believed to be a stress factor that can increase circulating levels of ACTH, cortisol, and other substances. 15,16) Repetitive blood sampling places subjects under artificial stress, and venipuncture as a stressor is useful for evaluation of the pharmacological effects of drug. 17)The purpose of this study was to determine the effects of domperidone on plasma levels of motilin-IS, somatostatin-IS, gastrin-IS, ACTH-IS, and cortisol in healthy individuals. MATERIALS AND METHODS SubjectsFive healthy male volunteers, aged 25-31 (median 28) years and weighing 54-70 (median 65.1) kg, particip...

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