Drotaverine - a Concealed Cytostatic!

Arch Pharm (Weinheim). 2017 Jan;350(1). doi: 10.1002/ardp.201600289. Epub 2016 Nov 23.

Abstract

Drotaverine (also known as dihydroperparine or No-Spa® ) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50 values as low as 3.0 μM were observed in SRB assays for HT-29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was observed after 24 h. Extra annexin V-FITC/PI assays and flow cytometry revealed drotaverine mainly to act as a cytostatic and only to a minor extent as cytotoxic agent.

Keywords: Cytostatic activity; Drotaverine; No-Spa®.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Humans
  • Mice
  • Papaverine / analogs & derivatives*
  • Papaverine / chemistry
  • Papaverine / pharmacology
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Antineoplastic Agents
  • Tetrahydroisoquinolines
  • drotaverin
  • Papaverine