Quantitative EEG and behavioral effects in volunteers of a new benzodiazepine (SAS 643) in relation to drug plasma concentration.

EEG (power spectral analysis) and behavioral effects of single, 5 to 20 mg doses of SAS 643, a newly developed benzodiazepine, were defined in normal male volunteers in relation to drug plasma concentration. A single 20 mg dose of SAS 643 induced an increment in power of fast frequency components (above 16.5 Hz), predominant on posterior leads, and paralleled by a decrement in the 4.5-8 Hz power. A concomitant increase in 0.5-4 Hz power and decrease in 8.5-12 Hz power were also evident in anterior scalp areas. EEG effects were less systematic following the administration 10 mg, and only occasional at the 5 mg dose. These EEG modifications are qualitatively consistent with the profile of antianxiety compounds, relative to dose and their ongoing time parallels SAS 643 plasma concentration, though the EEG/plasma level correlation was not statistically significant across subjects, due to individual variability. Systematic effects were not observed in any of the behavioral or neuropsychological variables considered. SAS 643 bioavailability and action at the central nervous system (CNS) level is established. The results exemplify the routine applicability of pharmaco-EEG procedures. The topographic differences in SAS 643 EEG effects warrant systematic studies on the issue.