Dose-dependent emetic effects of the Amaryllidaceous alkaloid lycorine in beagle dogs.
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.
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
Sascha
S
Kretzing
Getu
G
Abraham
Bettina
B
Seiwert
Fritz Rupert
FR
Ungemach
Ute
U
Krügel
Ralf
R
Regenthal
D047151:Amaryllidaceae Alkaloids / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D019963:Clinical Chemistry Tests; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004639:Emetics / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006207:Half-Life; D006403:Hematologic Tests; D019668:Liliaceae / Q000737:chemistry*; D008297:Male; D009325:Nausea / Q000139:chemically induced*; D010617:Phenanthridines / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D011446:Prospective Studies; D014839:Vomiting / Q000139:chemically induced*
D047151:Amaryllidaceae Alkaloids; D004639:Emetics; D010617:Phenanthridines; D010936:Plant Extracts; C015330:lycorine