Be¯oxatone is a new reversible and selective MAO-A inhibitor. The present study aimed to assess the pharmacodynamics (EEG pro®le and MAO-A inhibition using plasma levels of DHPG), pharmacokinetics and safety after a single dose of 10 mg of be¯oxatone compared to amitriptyline 50 mg in a randomized, double-blind, three-way crossover, placebo-controlled trial involving 12 elderly subjects. Be¯oxatone did not show any sedative pro®le on EEG as no signi®cant changes occurred in slow delta and theta waves or in alpha waves. In contrast, be¯oxatone produced a non-signi®cant decrease in delta relative power and a signi®cant increase in the (12±40 Hz) beta waves compared to placebo and/or amitriptyline depending on the EEG lead. MAO-A inhibition by be¯oxatone was evidenced by a signi®cant reduction in DHPG plasma levels (peak activity of À85 per cent and AUC 0±24 h of À46 per cent compared to placebo). The pharmacokinetics parameters obtained after a single 10-mg oral dose of be¯oxatone were: t max , 2 h; C max , 33 . 7 ng/ml; t 1a2 b, 14 . 5 h; AUC 0±I , 255 ng/ml for be¯oxatone and t max , 2 h; C max , 29 . 4 ng/ml; t 1a2 b, 16 h; AUC 0±I , 596 ng/ml for its main metabolite, O-demethyl be¯oxatone. These parameters are in the same range as those obtained in healthy young subjects. In conclusion, the present study demonstrated that a single oral dose of 10 mg of be¯oxatone is safe in the elderly, possesses potent MAO-A inhibition activity and the EEG pro®le of a non-sedative antidepressant and did not justify dose adjustment compared to young subjects.