Evaluation of xanthotoxol for central nervous system activity

J Ethnopharmacol. 1992 Jun;36(3):239-47. doi: 10.1016/0378-8741(92)90050-2.

Abstract

Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose-dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock-induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Cats
  • Conditioning, Psychological / drug effects
  • Cricetinae
  • Diazepam / pharmacology
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Furocoumarins / administration & dosage
  • Furocoumarins / pharmacology*
  • Furocoumarins / toxicity
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Rats
  • Reproduction / drug effects
  • Tranquilizing Agents / pharmacology*

Substances

  • Furocoumarins
  • Hypnotics and Sedatives
  • Tranquilizing Agents
  • xanthotoxol
  • Diazepam