Fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-
imidazole-2-yl)
urea] was suggested to possess
anxiolytic actions 30 years ago. Hoffmann-La Roche researchers recently reported that it is a selective and potent mGlu5 receptor antagonist, acting as a negative allosteric modulator. In the present study, we show that
fenobam readily penetrates to the brain, reaching concentrations over 600 nM, clearly above the affinity for mGluR5 receptors.
Fenobam (
at 10, 30, and 100 mg/kg) did not affect horizontal locomotor activity in the open field test.
Anxiolytic-like activity in the context freezing test was seen at 30 mg/kg, while
fenobam was not active in the elevated plus maze test at the tested concentrations.
Fenobam had antinociceptive actions in the
formalin test
at 10 and 30 mg/kg, but failed to attenuate
mechanical allodynia in the chronic constriction injury model. Impairment of learning was revealed in the passive avoidance test at 30 mg/kg.
Fenobam also impaired performance in both the Morris water maze and in the contextual fear conditioning test at the doses of 30 and 10 mg/kg, respectively. Prepulse inhibition, used as a model of psychomimetic activity, was not affected by
fenobam at doses of up to 60 mg/kg. Our results indicate that the beneficial effects of
fenobam occur in a similar dose range as the potential side-effects.