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  • Title: Effects of pirenzepine on Dai-kenchu-to-induced elevation of the plasma neuropeptide levels in humans.
    Author: Sato Y, Inoue S, Katagiri F, Itoh H, Takeyama M.
    Journal: Biol Pharm Bull; 2006 Jan; 29(1):166-71. PubMed ID: 16394532.
    Abstract:
    Dai-kenchu-to has been used for the treatment of abdominal obstructions, including bowel obstructions and a feeling of coldness in the abdomen. We reported that Dai-kenchu-to increases plasma neuropeptide [motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P]-like immunoreactive substances (IS) levels and that its pharmacologic effects on the gastrointestine are due to changes in gastrointestinal mucosa-regulatory peptide levels. We examined the effects of the selective M(1) muscarinic receptor antagonist pirenzepine on the elevation of Dai-kenchu-to-induced plasma neuropeptide (gastrin, motilin, somatostatin, VIP, CGRP, substance P)-IS levels in human volunteers and the area under the plasma neuropeptide concentration-time curve from 0 to 240 min (AUC(0-->240 min)), which were calculated from the plasma neuropeptide concentration-time curves from each volunteers. Oral pretreatment with pirenzepine reduced the Dai-kenchu-to-induced elevation of plasma motilin and VIP-IS levels and AUC(0-->240 min). Combined treatment with Dai-kenchu-to and pirenzepine increased plasma somatostatin-IS levels and decreased plasma gastrin-IS levels and had no effects on plasma CGRP- and substance P-IS levels and AUC(0-->240 min) compared with administration of Dai-kenchu-to alone. Dai-kenchu-to appeared to induce the release of motilin and VIP into plasma mainly through the activation of M(1) muscarinic receptors, and pirenzepine may affect the pharmacologic action of Dai-kenchu-to by elevation of plasma motilin and VIP levels.
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