[A unique psychopharmacologic profile of adrafinil in mice]

J Pharmacol. Jan-Mar 1986;17(1):37-52.
[Article in French]

Abstract

The following psychopharmacological effects of adrafinil have been observed in mice: increase in locomotor activity (64-256 mg.kg-1), antagonism (16-128 mg.kg-1) of the hypnotic effects of barbitone but not of pentobarbitone, reduction of immobility duration in the forced swimming test (16-256 mg.kg-1); slight antagonism (256 mg.kg-1) of electroshock-induced convulsions; no modification of rectal temperature; no stereotyped or climbing behaviour; no increase in lethality in aggregated mice (LD50 isolated = 1022 mg.kg-1, LD50 aggregated = 859 mg.kg-1); lack of effects on the provisional tests for antidepressants: no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia but potentiation of yohimbine-induced toxicity; lack of peripheral sympathetic effects (no mydriasis, no salivation, no contraction of the pilomotor muscles, no antagonism of reserpine-induced ptosis); lack of peripheral anticholinergic effects (no mydriasis, no antagonism of oxotremorine-induced salivation or lacrimation). As compared to no analeptic, anticholinergic or antidepressant drugs, adrafinil shows a unique behavioural profile in mice defined on the one hand by a specific stimulant activity associated with antidepressant-like effects that do no seem related to a beta-adrenergic mechanism and on the other hand by a lack of dopaminergic effects. Most adrafinil-induced effects (increase in locomotor activity, reduction of immobility duration in the forced swimming test) may correspond to a central alpha 1-adrenergic stimulation, but the unexpected lack of peripheral sympathetic effects remains unexplained.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Barbiturates / pharmacology
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Drug Interactions
  • Electroshock
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / pharmacology*
  • Hydroxamic Acids / toxicity
  • Male
  • Mice
  • Motor Activity / drug effects
  • Oxotremorine / pharmacology
  • Pupil / drug effects
  • Reserpine / pharmacology
  • Sleep / drug effects
  • Stereotyped Behavior / drug effects
  • Yohimbine / pharmacology

Substances

  • Barbiturates
  • Hydroxamic Acids
  • Yohimbine
  • Oxotremorine
  • Reserpine
  • adrafinil
  • Apomorphine