Effects of pirenzepine on Dai-kenchu-to-induced elevation of the plasma neuropeptide levels in humans

Biol Pharm Bull. 2006 Jan;29(1):166-71. doi: 10.1248/bpb.29.166.


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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Calcitonin Gene-Related Peptide / metabolism
  • Humans
  • Male
  • Motilin / metabolism
  • Muscarinic Antagonists / pharmacology*
  • Neuropeptides / blood*
  • Panax
  • Pirenzepine / pharmacology*
  • Plant Extracts / pharmacology*
  • Receptor, Muscarinic M1 / drug effects
  • Zanthoxylum
  • Zingiberaceae


  • Muscarinic Antagonists
  • Neuropeptides
  • Plant Extracts
  • Receptor, Muscarinic M1
  • dai-kenchu-to
  • Pirenzepine
  • Motilin
  • Calcitonin Gene-Related Peptide