Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping.
In a double-blind, placebo-controlled, cross-over study, the central effects of the natural molecule S-adenosyl-L-methionine (SAMe), or ademetionine (ADE), used in low doses as a nutraceutical and in higher doses as a pharmaceutical, were investigated by means of EEG mapping and psychometry. Ten young, normal healthy volunteers of both sexes, with a mean age of 25.2+3.9 yr received, in random order, infusions of 800 mg ADE in 250 ml of isotonic solution, and placebo consisting of 250 ml of isotonic solution administered over 30 min for 7 d, with a wash-out period of 3 wk in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 7. While there were no significant changes in psychometric findings, multivariate analyses of the EEG results based on MANOVA/Hotelling T 2 tests demonstrated significant encephalotropic effects of ADE compared to placebo. ADE-induced changes were characterized by a decrease in total power, an increase in absolute delta power and a decrease in absolute alpha and beta power, further by an increase in relative delta and beta power and a decrease in relative alpha power, a slowing of the delta/theta centroid, an acceleration of the alpha centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. Time-efficacy calculations demonstrated a significant central effect of ADE in the first hour after the first infusion, declining slowly until the third hour and thereafter steeply until the sixth hour; a further significant effect was after 1 wk of daily infusions and in the third hour after one superimposed infusion on day 7 of subacute treatment. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects at the neurophysiological level, underlying the antidepressant properties well-documented in clinical trials.
D000328:Adult; D000513:Alpha Rhythm / Q000187:drug effects; D000928:Antidepressive Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001611:Beta Rhythm / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011594:Psychometrics; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013997:Time Factors
D000928:Antidepressive Agents; D012436:S-Adenosylmethionine