title: Cognitive performance in elderly subjects after a single dose of befloxatone, a new reversible selective monoamine oxidase A inhibitor.
abstract: BACKGROUND
  Patients with depression often have cognitive and psychomotor performance impairments. Antidepressive treatments can correct these deficits, provided sedative and anticholinergic adverse effects do not add to the preexisting condition, particularly in elderly patients. Newly developed antidepressants therefore should be without deleterious effects on cognitive functions, including memory. Befloxatone is a new antidepressant with a potent, selective, competitive, and reversible inhibitory activity on the A isoform of monoamine oxidase (MAO-A).
  
  
  METHODS
  The effects on cognition and psychomotor performance of single oral doses of befloxatone (10 mg) and amitriptyline (50 mg) were compared in a randomized, double-blind, placebo-controlled, three-way crossover design trial in 12 healthy elderly (65 to 85 years) volunteers. The performances of the subjects were evaluated by a comprehensive battery of validated psychometric tests that explored alertness, psychomotor performance, information processing, and memory. Subjective feelings on mood and sleep were rated on visual analog scales. MAO-A inhibition was estimated by multiple titrations of 3,4-dihydrophenylglycol (DHPG) in plasma.
  
  
  RESULTS
  Amitriptyline displayed the expected deleterious effects on performance tasks, critical flicker fusion threshold, digit symbol substitution, and body sway, and it deteriorated memory (immediate and delayed free recall of words). In contrast, befloxatone did not impair cognition or psychomotor performance but instead significantly improved the delayed free recall. Amitriptyline adversely affected subjective feelings of alertness and contentedness, but befloxatone permitted sustained alertness and did not alter other subjective feelings or sleep. Concurrently, a single dose of 10 mg befloxatone markedly decreased the DHPG concentration in plasma.
  
  
  CONCLUSIONS
  Contrary to tricyclic antidepressants, whose deleterious effects are greater in elderly subjects, this study demonstrated the safety of befloxatone on cognition and psychomotor performance in elderly subjects.
authors.affiliation: Synthélabo Recherche, Clinical Development Department, Bagneux, France.
authors.forename: P
authors.initials: P
authors.lastname: Rosenzweig
authors.forename: A
authors.initials: A
authors.lastname: Patat
authors.forename: I
authors.initials: I
authors.lastname: Zieleniuk
authors.forename: I
authors.initials: I
authors.lastname: Cimarosti
authors.forename: H
authors.initials: H
authors.lastname: Allain
authors.forename: J M
authors.initials: JM
authors.lastname: Gandon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000639:Amitriptyline / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003863:Depression / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D012016:Reference Values
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D000639:Amitriptyline; C090014:befloxatone