Befloxatone (Synthelabo).

Synthelabo is developing befloxatone, a long-acting selective and reversible monoamine oxidase A (MAO-A) inhibitor, for the treatment of depression, social phobias and panic disorders. Phase III trials have commenced in France for depression. In 1995, phase II trials began in Europe and the US for the treatment of depression, social phobias and panic disorders. The results of a dose-ranging study conducted in Europe in patients with major depressive disorders confirmed the product's safety. Befloxatone has a good safety profile, lacking sedative, convulsant, anticholinergic and cardiovascular effects--particularly important is its negligible tyramine effect. Results from phase I trials suggest that it will be suitable for once-daily oral dosage. It has an elimination half-life of approximately 11 h in man and is rapidly absorbed with a Tmax of around 2.5 h. In a trial of befloxatone in 12 healthy elderly volunteers, an oral dose of 10 mg was administered and psychomotor and cognitive function were assessed using objective tests such as critical flicker fusion (CFF), body sway and learning memory tasks amongst others and subjective tests such as the visual analog scale and a sleep questionnaire. Using these criteria, the 10 mg dose of befloxatone was shown not to produce any detrimental effects in skilled performance while a significant improvement in long term memory was shown. It appears to have no significant effects on skilled performance, memory or sleep patterns. [11C]-befloxatone was evaluated and found to be an excellent ligand for the study of MAO-A by positron emission tomography.