Dose-dependent emetic effects of the Amaryllidaceous alkaloid lycorine in beagle dogs

Toxicon. 2011 Jan;57(1):117-24. doi: 10.1016/j.toxicon.2010.10.012. Epub 2010 Nov 3.

Abstract

Ingestions of plant material from Amaryllidaceae, especially the bulbs of daffodils, are known to be toxic, representing a persistent cause of poisoning in human and animals. Empiric data from case reports suggested, that the alkaloid lycorine could be the toxic constituent of the multi-component mixture responsible for symptoms like nausea and emesis. Systematic studies of the in vivo effects of the amaryllidaceaeous-type alkaloids are not available. Therefore, in an open, prospective, randomized and controlled trial we studied the dose-effect relationship of lycorine-induced nausea and emesis and the toxicokinetics of lycorine in beagle dogs. Subcutaneously administered lycorine-induced nausea and emesis starting at 0.5 mg/kg body weight reaching statistical significance at 1.0 mg/kg. The maximum emetic dose of lycorine (ED(100)) was 2 mg/kg body weight. There was a correlation between dose and nausea score as well as between dose and number of the induced emetic events. Nausea and emesis were short-lasting and occurred not later than 2.5 h post dose. Lycorine showed linear plasma kinetics with a mean elimination half-life of 0.67 and 0.3 h after single s.c. and i.v. administration, compatible with the clinical course of nausea and emesis. The mean oral bioavailability was calculated to be about 40%. Biochemical and haematological parameters of safety showed no pathological signs. The results provide evidence that lycorine can be considered as a main, if not the crucial constituent responsible for nausea and emesis in human and animals in poisoning due to ingestion of plant material of the Amaryllidaceae.

MeSH terms

  • Amaryllidaceae Alkaloids / blood
  • Amaryllidaceae Alkaloids / pharmacokinetics
  • Amaryllidaceae Alkaloids / toxicity*
  • Animals
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Clinical Chemistry Tests
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Emetics / blood
  • Emetics / pharmacokinetics
  • Emetics / toxicity*
  • Female
  • Half-Life
  • Hematologic Tests
  • Liliaceae / chemistry*
  • Male
  • Nausea / chemically induced*
  • Phenanthridines / blood
  • Phenanthridines / pharmacokinetics
  • Phenanthridines / toxicity*
  • Plant Extracts / blood
  • Plant Extracts / pharmacokinetics
  • Plant Extracts / toxicity
  • Prospective Studies
  • Vomiting / chemically induced*

Substances

  • Amaryllidaceae Alkaloids
  • Emetics
  • Phenanthridines
  • Plant Extracts
  • lycorine