A unique psychopharmacologic
profile of adrafinil in mice
by
Rambert FA, Pessonnier J,
de Sereville JE, Pointeau AM, Duteil J
J Pharmacol 1986 Jan-Mar; 17(1):37-52
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.
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