Acute effects of the anxiolytics suriclone and alprazolam on cognitive information processing utilizing topographic mapping of event-related brain potentials (P300) in healthy subjects

Abstract

In a double-blind, placebo-controlled, cross-over study, acute effects of suriclone--a cyclopyrrolone derivative--were investigated by means of topographic mapping of event-related potentials (ERPs). Fifteen normal volunteers, aged 22-35 years, received randomized, oral single doses of placebo, 0.1 mg, 0.2 mg and 0.4 mg suriclone and 1 mg alprazolam as a reference compound. ERPs were investigated in an auditory oddball paradigm before and 3 h after intake of each drug. In addition to 17 EEG leads, vertical and horizontal electro-oculograms (EOGs) were recorded. After EOG minimization and artifact identification, the peak latencies of the spatial average were determined by an automatic procedure. Compared to placebo, no significant effects of the low and middle doses of suriclone on N1 amplitude were observed; the highest dosage reduced N1 amplitude, as did 1 mg alprazolam to an even greater extent. While no consistent effects on P2 amplitude were observed after suriclone, alprazolam reduced P2 amplitude. P300 amplitude was reduced only after the highest dosage of suriclone, but much more so after alprazolam. P300 latency was not affected significantly by suriclone, but a marked prolongation of P300 latency was observed after 1 mg alprazolam. Concerning N1 and P2 effects, alprazolam, but not suriclone, may have an inhibitory influence on stimulus-induced cortical arousal. Concerning P300 effects, the used doses of suriclone were superior to 1 mg alprazolam, which seemed to have reduced cognitive information processing capacity and prolonged stimulus evaluation time. Self-rated well-being (adjective checklist) showed subtle beneficial effects after 0.1 mg and 0.2 mg, but marked sedative effects after both 0.4 mg suriclone and 1 mg alprazolam.

Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

“…This decrease could be easily detected since the N100m remained relatively stable over time in the control conditions. The finding of a N100m dipole moment decrease by lorazepam is well in line with earlier EEG (Rockstroh et al, 1991;Semlitsch et al, 1995) and MEG (Sinton et al, 1986) studies, reporting an N100/N100m amplitude decrease by benzodiazepine intake. Interestingly, no N100 amplitude reduction was observed in the study by Nakagome et al (1998), who revealed a reduction of the MMN as an overnight effect of triazolam intake.…”

“…Summing up the current and earlier reported effects of benzodiazepines on event-related potentials (ERPs), midlatency ERPs (including P50) seem to be unaffected by benzodiazepines (Schwender et al, 1993), while the amplitudes of most if not all long-latency ERPs are decreased (Milligan et al, 1989;Nichols and Martin, 1993;Rockstroh et al, 1991;Semlitsch et al, 1995). Besides an enforced inhibition of neural circuits involved in the MMN generation by GABAergic interneurons, the observed reduction of the MMN could also stem from an attenuated efficacy in sensory information processing, as reflected by the decreased N100m (as a bottom-up process).…”

“…Similarly, no difference in MMN was revealed between schizophrenic patients treated with high vs those with low doses of anxiolytic and hypnotic drugs, including benzodiazepines . A reduction of the MMN by benzodiazepines seems to be, nevertheless, likely to some extent, since a diminution of event-related components caused by benzodiazepines was found in several studies, as for the N100 (Rockstroh et al, 1991;Semlitsch et al, 1995), P200 (Semlitsch et al, 1995), and P300 (Milligan et al, 1989;Nichols and Martin 1993;Rockstroh et al, 1991;Semlitsch et al, 1995).…”

Overnight Effects of Triazolam on Cognitive Function: An Event-Related Potentials Study

“…These studies suggest detrimental effects of benzodiazepines on various stages of information processing, such as visual input [16][17][18], automatic feature registration [13,15], early stimulus discrimination [16], allocation of attention [13,15,18], usage of available processing capacity [15,16], context integration [13,14], central nervous system (CNS) excitability [17], cortical inhibition during memory consolidation [18], and recognition memory [19]. In those studies which adopted an auditory oddball task [20][21][22][23] as in this study, a significant reduction of P3 amplitude [20][21][22][23] was suggested, however, only one study suggested a reduction of N1 amplitude [20] and another study suggested a reduction in N2b amplitude [21] whereas no alteration was found in a third [22]. Prolongation of P3 latencies was reported in two studies [20,23] but not in two other studies [21,22], and only one study suggested a prolongation of N2b latencies.…”

“…In those studies which adopted an auditory oddball task [20][21][22][23] as in this study, a significant reduction of P3 amplitude [20][21][22][23] was suggested, however, only one study suggested a reduction of N1 amplitude [20] and another study suggested a reduction in N2b amplitude [21] whereas no alteration was found in a third [22]. Prolongation of P3 latencies was reported in two studies [20,23] but not in two other studies [21,22], and only one study suggested a prolongation of N2b latencies. Urata et al [23] conducted ERP recordings at multiple time points, such as 1, 2, 4, 6 and 8 h after triazolam administration and found that P3 amplitude was significantly reduced and P3 latency was significantly prolonged at 2 and 4 h after administration.…”