Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations.
In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of acutely and chronically administered milacemide--a new derivative of glycine showing anti-convulsant action by increasing GABA concentrations and endogenous glycine pools in the brain--were investigated in 12 elderly subjects in their late sixties. Each subject had a treatment period of 2 weeks (with 400 mg b.i.d. and 1,200 mg b.i.d. orally administered in week 1 and 2, respectively) and another period of 2 weeks with placebo. A treatment-free interval of 1 week was introduced in between. EEG-recordings, psychometric and psychophysiological tests as well as evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 2, 4, 6 and 8 after the administration of one single dose of 400 mg or placebo (acute effect), after 1 week's and 2 weeks' chronic administration (chronic effect), as well as after one additional superimposed dosage of 400 mg and 1,200 mg on days 8 and 15 of chronic treatment, respectively (super-imposed effect). Computer-assisted spectral analysis of the EEG demonstrated after single doses of 400 mg milacemide significant changes in the resting EEG indicative of improvement in vigilance (beta augmentation, acceleration of the beta centroid), while in the vigilance-controlled recording condition a dissociative vigilance shift occurred seen also after antidepressants of the amitriptyline and imipramine type (increase of both delta/theta and beta activity, decrease of alpha activity). One week chronic treatment resulted in the same V- and R-EEG profiles. However, after the 2nd weeks' treatment with higher doses as well as after one additional superimposed dosage of 1,200 mg milacemide both V- and R-EEG recordings demonstrated dissociative vigilance shifts. Time/treatment-efficacy calculations showed the chronic effect to be more pronounced than the acute effect, which peaked in the 2nd hour after oral drug administration. Psychometric analyses exhibited in noopsychic variables a significant improvement in intellectual and mnestic performance but even more so in the thymopsyche an improvement in subjective well-being and affectivity. Psychophysiological tests showed a decrease in CFF, while static and dynamic pupillometry and skin conductance measures remained unchanged. Pulse rate, systolic and diastolic blood pressure were not altered. The findings are discussed in the light of the involvement of GABA in the pathogenesis and treatment of affective disorders.
D000081:Acetamides / Q000494:pharmacology*; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D001611:Beta Rhythm; D001921:Brain / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D000081:Acetamides; D000927:Anticonvulsants; C039332:milacemide