EEG, MAO‐A inhibition, pharmacokinetics and safety of befloxatone in the elderly

Abstract

Befloxatone is a new reversible and selective MAO‐A inhibitor. The present study aimed to assess the pharmacodynamics (EEG profile and MAO‐A inhibition using plasma levels of DHPG), pharmacokinetics and safety after a single dose of 10 mg of befloxatone compared to amitriptyline 50 mg in a randomized, double‐blind, three‐way crossover, placebo‐controlled trial involving 12 elderly subjects. Befloxatone did not show any sedative profile on EEG as no significant changes occurred in slow delta and theta waves or in alpha waves. In contrast, befloxatone produced a non‐significant decrease in delta relative power and a significant increase in the (12–40 Hz) beta waves compared to placebo and/or amitriptyline depending on the EEG lead. MAO‐A inhibition by befloxatone was evidenced by a significant reduction in DHPG plasma levels (peak activity of −85 per cent and AUC0–24 h of −46 per cent compared to placebo). The pharmacokinetics parameters obtained after a single 10‐mg oral dose of befloxatone were: tmax, 2 h; Cmax, 33·7 ng/ml; t1/2β, 14·5 h; AUC0–∞, 255 ng/ml for befloxatone and tmax, 2 h; Cmax, 29·4 ng/ml; t1/2β, 16 h; AUC0–∞, 596 ng/ml for its main metabolite, O‐demethyl befloxatone. 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 befloxatone is safe in the elderly, possesses potent MAO‐A inhibition activity and the EEG profile of a non‐sedative antidepressant and did not justify dose adjustment compared to young subjects. © 1997 John Wiley & Sons, Ltd.

Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients

“…The number of subjects was evaluated according to other studies using the same Methology/tests, evaluation, etc. [23,24].…”

“…In the present study, EEG modifications were found with nicardipine. This method is frequently used to assess the effects of psychotropic drugs [23,24] but apparently has never been applied to hypertensive patients, to evaluate the effects of antihypertensive drugs on cognitive functions. Nicardipine induces a psycho‐stimulant profile (decrease of slow delta waves and increase of alpha energy power).…”

“…Artefact‐free 5‐, 10‐ and 20‐s recordings were submitted to spectral analysis and fast Fourier transform (FFT) using the Cooley Tuckey algorithm and application of Walsh ponderation. For each epoch, total energy, standard deviation and delta (0–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta 1 (12–12 Hz), beta 2 (16–20 Hz) and beta 3 (20–30, 30–40 and 40–50 Hz) relative power expressed as percentages of total energy were calculated and averaged [24].…”

The separate and combined effects of monoamine oxidase A inhibition and nicotine on resting state EEG

“…However, high doses of befloxatone also increased theta power, inconsistent with EEG profiles of smoking. Befloxatone has also been shown to increase beta power compared to placebo in elderly subjects (Patat et al, 1997). One interesting study examined the relationship between frontal midline theta activity and platelet MAO in healthy males (Hashimoto et al, 1988), and found a negative correlation between the two measures.…”