Blood levels and electroencephalographic effects of diazepam and bromazepam

Abstract

Blood levels and electroencephalographic (EEG) data were collected for 2 hr after single oral doses of bromazepam (9 mg), diazepam (10 mg), and placebo in 13 male adult volunteers. Both drugs caused an increase in beta activity (above 13 Hz) and a decrease in alpha activity (9 to 11 Hz) in the EEG. Blood levels of 100 ng/ml of diazepam or 50 ng/ml of bromazepam were associated with significant changes in EEG beta activity. Temporal changes in the EEG after administration of diazepam or bromazepam paralleled development of plasma levels of these drugs. Although a weakly significant correlation was found between measurable diazepam blood levels and amount of increased EEG beta activity, the relationship between measurable bromazepam blood levels and the degree of EEG changes was not significant. Quantitative EEG is a sensitive continuous response measure, useful in defining cerebral activity, response latency, and relative potency of psychoactive benzodiazepines.

Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers

“…This difference in sensitivity may be due to cancellation of base-line¯uctuations, as both the negative and positive peaks would be equally affected by such¯uctuations. The vertex electrode (Cz) was found to be the most sensitive scalp location for the evaluation of the effect of diazepam, which is consistent with literature reports [3,9].…”

“…diazepam, whereas the serum diazepam concentration shows a corresponding decrease to about one third of the initial concentration. This indicates that changes in the ERPs following diazepam administration do not directly re¯ect the blood concentration of the drug, as suggested previously [9]. A more likely explanation is that diazepam, which is a very lipophilic substance, progressively distributes into the fatty tissue of the brain as the serum concentration falls, resulting in a delayed pharmacodynamic effect.…”

“…Fink et al [9] found a linear correlation between the increase in EEG and beta-activity and blood concentrations of diazepam after oral administration to healthy volunteers. More recent studies of the pharmacological effects of benzodiazepines in man have been of nonblinded design, and only 3 out of 18 were controlled, emphasizing the need for additional well designed studies in this ®eld [11].…”

The influence of bromazepam on cortical power distribution

“…Since the late 1960's it has been reported that the intake of benzodiazepines generates a typical anxiolytic pharmaco-EEG profile, which is characterized by increased beta and decreased alpha activity (Saletu et al 1989, 1986, Herrmann 1982, Itil 1974 Devos 1976). Saletu et al (1986) and Fink et al (1976) observed this specific pattern using higher dosages in their studies (diazepam 10 mg and bromazepam 9 mg). In addition, studies have shown that bromazepam does not induce augmentation of slow waves in the clinical dosage range, even if they are administered in extremely high doses (Saletu et al 2002).…”

“…One of the few studies that examined the effects of this particular drug on qEEG was conducted by Fink et al (1976). The effects of single oral doses of bromazepam (9 mg) and diazepam (10 mg) in EEG data were analyzed for thirteen male adult volunteers and an analogous result was reached: increased beta and decreased alpha activity.…”