title: Effects of pirenzepine on Dai-kenchu-to-induced elevation of the plasma neuropeptide levels in humans.
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.
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Oita, Japan. syuhki@med.oita-u.ac.jp
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sato
authors.forename: Shin
authors.initials: S
authors.lastname: Inoue
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Hiroki
authors.initials: H
authors.lastname: Itoh
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takeyama
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006801:Humans; D008297:Male; D009037:Motilin / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009479:Neuropeptides / Q000097:blood*; D005894:Panax; D010890:Pirenzepine / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D032106:Zanthoxylum; D030521:Zingiberaceae
chemical_list: D018727:Muscarinic Antagonists; D009479:Neuropeptides; D010936:Plant Extracts; D043643:Receptor, Muscarinic M1; C121414:dai-kenchu-to; D010890:Pirenzepine; D009037:Motilin; D015740:Calcitonin Gene-Related Peptide