The Japanese herbal medicine (Kampo) Ninjinto has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. The pharmacological effects of Ninjinto on the gastrointestine are due to changes in the levels of gut-regulated peptide, such as motilin, somatostatin, calcitonin gene-related peptide (CGRP), substance P, and vasoactive intestinal polypeptide (VIP). The release of these peptides is controlled by acetylcholine (ACh) from the preganglionic fibers of the parasympathetic nerve. Thus, we examined the effects of the selective M1 muscarinic receptor antagonist pirenzepine on the elevation of Ninjinto-induced plasma the area under the plasma gut-regulated peptide concentration-time curve from 0 to 240？min ( ) in humans. Oral pretreatment with pirenzepine significantly reduced the Ninjinto-induced elevation of plasma motilin and substance P release ( ). Combined treatment with Ninjinto and pirenzepine significantly increased the release of plasma somatostatin ( ) compared with administration of Ninjinto alone or placebo. Ninjinto appeared to induce the release of substance P and motilin into plasma mainly through the activation of M1 muscarinic receptors, and pirenzepine may affect the pharmacologic action of Ninjinto by the elevation of plasma substance P, motilin, and somatostatin. 1. Introduction Kampo medicines, traditional herbal medicines, have been employed for a few thousand years and have contributed greatly to the treatment of many subjective symptoms. Kampo medicines are frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases. Such herbal medicines have been used in China for thousands of years and are now being manufactured in Japan as drugs. Most Kampo medicines are prepared from multiple crude herbs and contain many unrefined substances, and to determine the precise mechanism of the pharmacological effects of these medicines is too difficult. Ninjinto, a traditional Japanese Kampo medicine, is prepared from four different Chinese crude drugs. This medicine is one of the major prescriptions most frequently used for treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia in Japan. Al previous study has shown that Ninjinto not only significantly improved gastrointestinal motility but also showed stronger effects than those of some prokinetic drugs such as cisapride and metoclopramide in a rat model of postoperative ileus [1]. Hence, Ninjinto may be an effective herbal medicine for
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