mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I)

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83. doi: 10.1016/j.bmcl.2009.08.016. Epub 2009 Aug 8.

Abstract

Novel compounds were prepared that united the pharmacologies of the mu-opioid tramadol with the 5-HT4 agonists metoclopramide and norcisapride. The synthesis, chiral separation and in vitro activity of the new compounds is described.

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / chemistry*
  • Analgesics, Opioid / pharmacology
  • Cisapride / analogs & derivatives
  • Cisapride / chemistry
  • Cisapride / pharmacology
  • Gastrointestinal Transit / drug effects
  • Humans
  • Metoclopramide / chemistry
  • Metoclopramide / pharmacology
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / metabolism
  • Receptors, Serotonin, 5-HT4 / metabolism
  • Respiratory System / drug effects
  • Serotonin 5-HT4 Receptor Agonists*
  • Stereoisomerism
  • Tramadol / chemistry

Substances

  • Analgesics, Opioid
  • Receptors, Opioid, mu
  • Serotonin 5-HT4 Receptor Agonists
  • norcisapride
  • Receptors, Serotonin, 5-HT4
  • Tramadol
  • Metoclopramide
  • Cisapride