Effects of short-term treatment with befuraline on sleep and REM-inducing activity of physostigmine

Befuraline is a new antidepressant compound active in some animal models of depression and in human affective disorders. It is a direct adrenergic agonist and an inhibitor of norepinephrine and serotonin uptake and cyclic adenosine monophosphate phosphodiesterase activity. It has no central anticholinergic properties. Its effects on nocturnal sleep and rapid-eye-movement (REM)-inducing action of physostigmine were investigated in eight young male volunteers after one week of treatment with 50 mg BID. The results of the study show that befuraline increases REM latency without significantly modifying other REM and non-REM sleep parameters. These findings indicate that befuraline, as the other antidepressant drugs, has REM suppressant activity, perhaps only partially revealed by our study because of its short term and low dosage and because it was performed in healthy subjects. However, befuraline successfully counteracts the REM-inducing action of physostigmine since the latter cannot further decrease REM latency after one week of treatment. Both these results confirm the experimental data on the lack of central anticholinergic properties of befuraline and indicate that at least some biochemical mechanisms of the drug are already active after one week of treatment.