The Noscapine Chronicle: A Pharmaco-Historic Biography of the Opiate Alkaloid Family and its Clinical Applications

Med Res Rev. 2015 Sep;35(5):1072-96. doi: 10.1002/med.21357. Epub 2015 Jul 14.

Abstract

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.

Keywords: antineoplastic drugs; centrosome declustering drugs; microtubule targeting drugs; noscapine; noscapinoids.

Publication types

  • Review

MeSH terms

  • Alkaloids / chemistry*
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Centrosome / drug effects
  • Chemistry, Pharmaceutical / methods
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Male
  • Microtubules / drug effects
  • Neoplasms / drug therapy
  • Noscapine / chemistry*
  • Papaver
  • Plant Extracts
  • Stroke / drug therapy
  • Warfarin / administration & dosage

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Plant Extracts
  • Warfarin
  • Noscapine