Behavioural profiles of the reversible monoamine-oxidase-A inhibitors befloxatone and moclobemide in an experimental model for screening anxiolytic and anti-panic drugs

Abstract

The present study compared the behavioural effects of acute and chronic (one daily i.p. injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) and befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDTB) which has been designed for screening anxiolytic and anti-panic drugs. In the MDTB, Swiss mice were confronted with a natural threat (a rat) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flight, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behaviours were observed. This was in contrast to chronic treatments, where moclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a significant reduction in one flight measure (avoidance distance when the rat was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but not moclobemide, increased RA responses when mice were constrained in one part of the apparatus facing the rat, which remained at a constant distance. No other drug effects were observed with either compound. Although these behavioural profiles are consistent with an anxiolytic-like effect, the finding of an action upon a limited number of defence responses suggests a weaker anxiolytic-like potential compared to that of classical anxiolytics. However, in view of previous data with panic-modulating compounds on flight behaviours in the MDTB, the present results are in line with clinical results showing that moclobemide is effective in panic disorders and suggest that befloxatone may have some efficacy in the clinical management of panic.

Flavonoids from Tilia americana with anxiolytic activity in plus-maze test

“…It has also been demonstrated that the flavonol termed kaempherol, as well as the two mentioned flavones mentioned previously, act as monoamineoxidase A and B (MAO A and B) inhibitors (Sloley et al, 2000). There are reports indicating that substances with these abilities on MAO -as in the case of phenelzine, befloxatone, and mocloben -modulate monoamine levels in brain (serotonine, dopamine, and norepinephrine) and provoke behavioral modifications in rodents, indicating an anxiolytic effect (Griebel et al, 1997(Griebel et al, , 1998.…”

Anxiolytic effect of berberine on exploratory activity of the mouse in two experimental anxiety models: Interaction with drugs acting at 5-HT receptors

“…Moclobemide, a MAOI drug, after chronic administration produces anxiolytic effects in mice (De Angelis and Furlan, 2000) by decreasing the levels of monoamines and increasing the turnover rates of monoamines (Griebel et al, 1997). Moreover, jatrorrhizine and BER were found to inhibit MAO-A (Kong et al, 2001).…”

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

“…alprazolam and clonazepam) and chronic treatments with various antidepressants (i.e. imipramine,¯uoxetine, moclobemide and phenelzine), reduced¯ight behavior [12,48,49,51]. In contrast, drug challenges known to trigger or potentiate human panic responses such as acute imipramine,¯uoxetine, yohimbine or the BZ receptor antagonist¯umazenil [27,54,55,90] were found to increase¯ight [16,48].…”