Biomedical subjects

P Anderer

Publications and source records attributed to P Anderer.

At least 55 records · Page 3Linked to original sources

PubMed1997

Nonorganic insomnia in generalized anxiety disorder. 2. Comparative studies on sleep, awakening, daytime vigilance and anxiety under lorazepam plus diphenhydramine (Somnium) versus lorazepam alone, utilizing clinical, polysomnographic and EEG mapping methods.

Previous human pharmacological and toxicological studies demonstrated advantages of the combination drug Somnium [SOM, lorazepam (LOR) 1 mg plus diphenhydramine 25 mg] over 1 mg LOR alone, as it showed synergistic effects in hypnotic properties and antagonistic effects in regard to toxicity. In the present double-blind, parallel-group study, hypnotic and anxiolytic effects of SOM were studied in 44 patients with non-organic insomnia related to mild generalized anxiety disorder (GAD), as compared with LOR alone. After a placebo run-in phase of 1 week, they received active treatment (1 tablet SOM or LOR 1 mg) for 4 weeks and thereafter placebo again for 1 week. Clinical evaluations included the physician's general assessment of efficacy, tolerance and adverse effects, the Hamilton anxiety rating scale (HAMA), the Zung self-rating anxiety scale (SAS) and depression scale, the withdrawal symptom scale (WSS), hematology and blood chemistry. Sleep laboratory evaluations included objective and subjective sleep and awakening quality, measured by polysomnography, self-rating of sleep and awakening quality (SSA) and a psychometric test battery in the morning, as well as measurement of daytime brain function, objectivated by EEG mapping. Physicians' global evaluation of insomnia demonstrated no changes in the pre-drug placebo period, moderate improvement under both drugs, with a marginal advantage of SOM over LOR in the first 2 weeks, and a return to pre-drug values in the post-drug placebo period. Anxiety improved in observer ratings (HAMA) under both drugs, in self-rating (SAS) under the combination drug only, with the scores returning to pre-drug placebo values after post-drug placebo substitution. There were no significant findings in the self-rating depression scale and the WSS, with the exception of an improvement in the WSS score 4 weeks after SOM, as compared with pre-drug placebo. There were no rebound phenomena. Both drugs were well tolerated-in regard to both adverse effects and laboratory findings. Confirmatory statistics on the polysomnographically recorded target variable latency to sleep onset stage 2 demonstrated a significant shortening of sleep latency after SOM and a significant superiority of the combination drug SOM over LOR after acute dosing, as compared with pre-drug placebo. Descriptive statistics demonstrated further a significant improvement of sleep efficiency and total sleep time after SOM and of wakefulness time and number of awakenings during the total sleep period after both drugs, but no interdrug differences. Sleep architecture remained unchanged. Subjective sleep quality improved with both drugs, morning drowsiness and the total SSA score only with SOM, while LOR was superior to SOM regarding morning somatic complaints. There were neither changes nor interdrug differences in the morning noopsyche. In psychophysiology, critical flicker frequency decreased more under SOM than LOR. After 4 weeks therapy, no significant findings in polysomnography and subjective sleep and awakening were seen, except for an increase in movement time under LOR (tolerance development). In objective awakening quality, psychometry revealed an improvement of reaction time under SOM and a decrease of attention variability and an increase in fine-motor activity under LOR, with an interdrug comparison showing a significant superiority of SOM over LOR in regard to reaction time, reaction time variability and reaction time performance. After placebo substitution, rebound phenomena were seen in polysomnography and subjective sleep and awakening in the 1st night of the SOM group only, which were gone in the 7th placebo night, however. Noopsychic performance remained improved in both groups, with a superiority of SOM to LOR in regard to reaction time and reaction time variability. (ABSTRACT TRUNCATED)

Adult↗

PubMed1996

Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and -inhibiting fluvoxamine utilizing EEG mapping and psychometry.

In a double-blind, placebo-controlled study, the encephalotropic and psychotropic effects of tianeptine (TIA)--a new tricyclic antidepressant, enhancing serotonin reuptake--were investigated as compared with the serotonin reuptake inhibiting antidepressant, fluvoxamine (FLU), utilizing EEG mapping, psychometric and psychophysiological measures. 16 healthy volunteers (8 males, 8 females) aged 21-35 (man 27) years received randomized and at weekly intervals single oral doses of placebo, 12.5 and 25 mg TIA and 50 mg FLU. EEG recordings, psychometric and psychophysiological tests and evaluation of pulse, blood pressure and side effects were carried out at 0, 2, 4, 6 and 8 hours; blood sampling, in addition, at hour 1. TIA plasma levels rose fast to peaks at 1-2 hours and declined rapidly as well, while the MC5 metabolite peaked in the 4th hour and declined more slowly. EEG mapping demonstrated that both TIA and FLU induced significant changes in brain function between the 1st and 8th hour, which, however, differed in their time course. 12.5 mg TIA exhibited, as compared with placebo, slight activating properties in the EEG (decrease of delta and theta, increase of alpha and beta, acceleration of the centroid), parallelled by thymopsychic improvement (mood elevation). 25 mg TIA showed EEG activation up to the 4th hour, later EEG sedation, accompanied by an initial thymopsychic improvement and differential changes thereafter (improved mood, decreased vigility), with the noopsyche improving at all times (attention, Pauli test). 50 mg FLU induced initially sedation and thereafter activation, accompanied by thymopsychic deterioration and subsequent improvement, the latter also being observed in the noopsyche (attention, memory). In pupillary and skin conductance measures, generally a slight activation occurred after placebo, which was attenuated by 25 mg TIA. Correlation maps between plasma levels and EEG changes demonstrated: the higher the TIA plasma levels, the more absolute and relative beta power, the less alpha power and the faster the centroid of the total power spectrum, reflecting CNS-activation. Topographically, the correlations were mostly seen over both fronto-temporal regions. In the latter, dominant frequency signalled desactivation in the right and activation in the left hemiphere after both antidepressants which, thereby induced changes in brain function opposite to those observed in depression. Both drugs were well tolerated.

Adult↗

PubMed1996

Severe hypoglycaemia unawareness is associated with an early decrease in vigilance during hypoglycaemia.

To elucidate neurophysiological characteristics in hypoglycaemia unawareness, we investigated the relationship between electroencephalography (EEG) parameters of vigilance and awareness of various symptom categories early in response to hypoglycaemia in intensively treated diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/1) was induced with an intravenous insulin bolus in seven patients with insulin-dependent diabetes mellitus (IDDM) with a history of hypoglycaemia unawareness and repeated severe hypoglycaemia, as well as in a group of seven IDDM patients with good awareness of hypoglycaemia. Both groups were comparable in age, treatment strategy, glycaemic control and level of late complications. Basic cognitive performance and other symptom categories were estimated serially during a period of 2 h following the insulin bolus. A vigilance-controlled EEG was recorded continuously; its automatic analysis included the evaluation of vigilance indices. In the baseline prehypoglycaemic state, hypoglycaemia unaware patients showed higher initial vigilance (p = .05) than the aware group. Unaware patients reported fewer neurogenic (p = .002, mainly cholinergic, p = .009) hypoglycaemia symptoms during hypoglycaemia, and developed an impairment in cognitive performance over time (p = .002). EEG analysis indicated a more rapid decrease in vigilance after the hypoglycaemic stimulus for unaware patients than for aware patients. The lowering of plasma glucose to 3.06-3.89 mmol/l already induced a significant increase in delta and theta, as well as a decrease in alpha relative power only in the unaware group. Differences between groups with regards to the degree of deceleration were most pronounced early, during only slight hypoglycaemia, and topographically spread over central and parietal brain regions. Further lowering of plasma glucose induced an even more pronounced, abrupt increase in slow waves in unaware patients at higher plasma glucose levels than in hypoglycaemia aware subjects (for delta waves at 2.41 +/- 0.16 vs. 1.96 +/- 0.1 mmol/l, p = .04). This preceded the worsening of cognitive performance during hypoglycaemia in unaware patients by 19 +/- 3 min. Hypoglycaemia unawareness associated with previous unconsciousness is associated with- and may be the result of-an early hypoglycaemia-induced reduction in vigilance and an early EEG deceleration, which seems to be a teleologically effective measure for delaying eventual cerebral energy failure in hypoglycaemia.

Adult↗

PubMed1996

Hormonal, syndromal and EEG mapping studies in menopausal syndrome patients with and without depression as compared with controls.

UNLABELLED: The aim of the study was to investigate brain function in menopausal depression by EEG mapping, as compared with menopausal syndrome patients without depression and normal controls, and to correlate neurophysiological with clinical and hormonal findings in order to elucidate the pathogenesis of depression in the menopause. METHODS: One hundred and twenty-nine menopausal women, aged 45-60 years, with no previous hormonal replacement therapy were investigated in regard to hormones (estradiol [E2], follicle stimulating hormone [FSH]), clinical symptomatology (Kupperman Index [KI], Hamilton depression score [HAMD]) and brain function (EEG mapping). Based on KI and DSM-III-R research criteria for major depression, 3 groups were available for statistics (after removal of protocol violators): group A had a KI of <15 and no depression (n = 29); group B had a KI of > or = 15 and no depression (n = 29) and group C had a KI of > or = 15 and fulfilled the criteria for major depression (n = 60). RESULTS: EEG maps of depressed patients demonstrated less total power and absolute power in the delta, theta and beta band, more relative delta and less alpha power as well as a slower delta/theta and faster alpha and beta centroid than controls, suggesting a vigilance decrement. Group B did not differ from group A. Correlation maps showed significant relationships between estradiol levels and EEG measures (the lower the E2, the worse the vigilance) and between the EEG measures and the Hamilton depression (HAMD) score (the worse the vigilance, the higher the depression score). There were no correlations between the hormones E2 and FSH and the syndromes KI and HAMD. In the target variable, the asymmetry index, depressed patients showed less alpha power over the right than left frontal lobe, whereas normal controls exhibited the opposite. Group B did not differ from group A. The frontal asymmetry index was significantly correlated with the Hamilton depression score and suggests right frontal hyper- and left frontal hypoactivation in depression. CONCLUSIONS: Although hormonal findings are not directly linked to psychic changes, low estradiol levels do contribute to a decreased vigilance at the neurophysiological level , which is in turn correlated with higher depressive and menopausal symptomatology at the behavioural level. Depression is further correlated to a right frontal hyper- and left frontal hypoactivation.

Brain↗

PubMed1996

Multichannel auditory event-related brain potentials: effects of normal aging on the scalp distribution of N1, P2, N2 and P300 latencies and amplitudes.

Event-related potentials (ERPs) were recorded at 17 leads in an auditory oddball paradigm in 172 normal healthy subjects aged between 20 and 88 years. With advancing age, N1 latency increased parietally (0.12 ms/year), P2 latency increased frontally (0.34 ms/ year) and N2 and P300 latencies increased all over the scalp (0.37 ms/year for N2; 0.92 ms/year for P300). P300 latency/age relationship was curvilinear with accelerated latency increase in elderlies (0.35 ms/year for subjects below 60 years; versus 2.03 ms/year for subjects above 60 years). With advancing age, standard tone ERP amplitudes were enhanced frontally (0.03 microV/year for N1; 0.07 microV/year for P2), N2 amplitudes were attenuated frontally (0.11 microV/year) and P300 amplitudes were attenuated parietally (0.15 microV/year). Multichannel analysis demonstrated that ERP latencies and amplitudes depended on electrode location. Standard tone ERP latencies changed their topographic distribution with age, whereas target tone ERP latencies did not. While N1 amplitude distribution was unaffected by age, P2, N2 and P300 topography changed significantly with age: P2 topography to a more frontal distribution and increased 'global field power'; N2 topography to a more parietal distribution: P300 topography to a more frontal and more equipotential distribution Thus, specific age effects on different ERP components were confirmed.

Acoustic Stimulation↗

PubMed1996

On the cerebro-protective effects of caroverine, a calcium-channel blocker and antiglutamatergic drug: double-blind, placebo-controlled, EEG mapping and psychometric studies under hypoxia.

1. In a double-blind, placebo-controlled study, the acute antihypoxidotic properties of the calcium-channel blocking and antiglutamatergic caroverine were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. 2. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found in 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 16 healthy, young volunteers. They received randomized after an adaptation session, single oral doses of placebo, 40, 80 and 120 mg caroverine. Evaluation of blood gases, EEG mapping and psychometry were carried out 0, 2, 4, 6 and 8 h post-drug, during hypoxia. 3. Blood gas analysis demonstrated a drop in PO2 from 95 to 33 and 30 mmHg, in PCO2 from 38 to 30 and 30 mmHg in the 14th and 23rd minute of inhalation, respectively, while pH increased from 7.41 to 7.50 and 7.51. Base excess and standard bicarbonate remained stable. 4. EEG mapping under hypoxia exhibited a marked increase of delta/theta, decrease of alpha and an increase of superimposed beta activity, which reflects deterioration of vigilance. 5. Caroverine attenuated this hypoxia-induced vigilance decrement in a dose- and time-dependent manner 6-8 h after 80 mg and 2-8 h after 120 mg. 6. Hypoxic hypoxidosis induced a deterioration of memory and attention variability, which was mitigated by 80 and 120 mg caroverine. However, there was an augmentation of the hypoxia-induced decrement in psychomotor performance after 120 mg. 7. The drug was well tolerated, and there were no significant differences compared with placebo with regard to pulse and blood pressure.

Adult↗

PubMed1996

EEG topography during insulin-induced hypoglycemia in patients with insulin-dependent diabetes mellitus.

A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8 men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under normoglycemic and hypoglycemic conditions (glucose levels after intravenous insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia, a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and especially in theta activity (p < 0.05) were found. The most sensitive parameter was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the increase in delta and theta activity showed a topographic maximum in lateral frontal regions. During deep hypoglycemia there was a topographic maximum of slow frequencies in posterior parts of the brain (centrotemporal to parieto-occipital regions). The differences between the group with good and with poor awareness of hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p < 0.05). At lower glucose levels group distinction was no longer possible. These EEG changes correspond to a temporary organic brain syndrome.

Adult↗

PubMed1996

First-night-effects on generalized anxiety disorder (GAD)-based insomnia: laboratory versus home sleep recordings.

First-night effects (FNE) were comparatively investigated in patients with disorders in initiating and maintaining sleep (DIMS) associated with generalized anxiety disorder (GAD) in laboratory (n = 22) and home sleep polysomnography (n = 21). Patients had to be drug-free for at least 2 weeks prior to the first recording. Evaluation measures included 1) objective data on sleep initiation and maintenance; 2) sleep architecture based on polysomnographic recordings, analyzed visually according to the criteria of Rechtschaffen and Kales; 3) subjectively estimated sleep and awakening quality, assessed by a self-rating scale and visual analogue scales; 4) objective awakening quality as measured by a psychometric test battery; and 5) psychophysiological data, including critical flicker frequency, muscle strength, pulse, and blood pressure. Statistical analysis using multivariate analysis of variance (MANOVA) demonstrated multiple FNE in both groups regarding sleep efficiency, total sleep time, percentage of time in stage 2 sleep, percentage of time in stage 3/4 sleep, minutes of rapid eye movement (REM) sleep, and REM sleep latency. There was a group-by-night effect in the number of awakenings. There were no significant FNE regarding subjective sleep and awakening quality in either group. Differential adaptation effects were observed in attention and fine motor activity, with improvement in laboratory-recorded patients and deterioration in home-recorded patients. Differential findings also occurred in regard to evening blood pressure, with laboratory-recorded patients showing more adaptation.

Adult↗

PubMed1995

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

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.

Adult↗

PubMed1995

Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebo-controlled, clinical and EEG/ERP mapping study.

In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multiinfarct dementia (MID), based on computed tomography and Hachinski scores (< or = 49 SDAT, > or = 7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC. SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable-the Clinical Global Impression (CGI)-a significant superiority of Global Impression (CGI)-a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (chi 2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (chi 2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.

Alzheimer Disease↗

PubMed1995

Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression.

In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.

Administration, Cutaneous↗

PubMed1995

Cognitive psychophysiology in nootropic drug research: effects of Ginkgo biloba on event-related potentials (P300) in age-associated memory impairment.

Extracts from the leaves of Ginkgo biloba have been suggested to be useful in the treatment of various symptoms of impaired brain functions in advanced age. To elucidate specific mechanisms of the possible clinical benefit, the effects of Ginkgo biloba extract Ginkobene on cognitive information-processing were investigated by means of long-latency auditory event-related potentials. In a double-blind placebo-controlled study, 48 patients (29 women and 19 men) aged between 51 and 79 years with the diagnosis of age-associated memory impairment had 57 days' treatment with a daily dosage of 3 x 40 mg Ginkobene or placebo. To evaluate acute, chronic, and superimposed drug effects, psychophysiological investigations were carried out on day 1 and day 57 before and 3 hours after drug administration. ERP investigations were carried out by means of a two-tone auditory oddball paradigm. In addition to 17 EEG leads, vertical and horizontal EOGs were recorded. After minimizing ocular artifacts and visual artifact rejection, latencies and topographic distributions of N1 and P2 components (non-targets) and N2 and P300 components (targets) were calculated by an automatic procedure. When compared to the placebo group, in the Ginkobene group no consistent and unequivocal changes on N1, P2, N2, and P300 amplitudes or on N1, P2, and N2 latencies were observed. P300 latency was shortened by 31 ms, 38 ms, and 32 ms in the Ginkgo biloba group after acute, chronic, and superimposed drug administration. It may therefore be hypothesized that the decrease of P300 latency in the Ginkgo biloba group may reflect shorter stimulus-evaluation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗

PubMed1995

Double-blind, placebo-controlled, pharmacokinetic and -dynamic studies with 2 new formulations of piracetam (infusion and sirup) under hypoxia in man.

In a double-blind, placebo-controlled study, pharmacokinetics and pharmacodynamics of 12 g piracetam in 2 different formulations were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2, found in 6,000 m altitude), which was inhaled for 23 minutes under normobraic conditions by 18 healthy volunteers. They received after an adaptation session randomized at weekly intervals 12 g piracetam i.v. (250 ml infusion over 30 minutes), 12 g piracetam p.o. (60 ml sirup) and placebo. Blood levels were determined by means of an HPLC at the hours 0, 1, 2, 4, 6, 8 and 24. The 2 formulations showed a very similar time-course, with slightly higher blood levels in the 1st hour after the intravenous than oral administration, and vice versa thereafter. The elimination half-life was 4.3 hours for both formulations, the area under the curve and the clearance value were also almost identical. Evaluation of blood gases, EEG mapping and psychometry were carried out at 0, 2, 4, 6 and 8 hours post-drug. Blood gas analysis demonstrated a drop in SaO2 from 99 to 73 and 70%, in PO2 from 100 to 35 and 33 mmHg, in PCO2 from 36 to 31 and 31 mmHg in the 14th and 23rd minute of inhalation, respectively. pH increased from 7.43 to 7.48 in the respective minutes, while base excess and standard bicarbonate remained stable. EEG mapping exhibited under hypoxia a marked increase of total power, mostly due to an augmentation of delta/theta, and a decrease of alpha activity, which reflects deterioration of vigilance. Both piracetam preparations significantly attenuated this vigilance decrement, with 12 g piracetam i.v. showing its encephalotropic peak effects in the earlier hours, 12 g piracetam sirup in the later hours. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noo- and thymopsyche, which was mitigated by both piracetam preparations, mostly in the 6th hour. Both formulations were well tolerated.

Administration, Oral↗

PubMed1995

Acute central effects of the calcium channel blocker and antiglutamatergic drug caroverine. Double-blind, placebo-controlled, EEG mapping and psychometric studies after intravenous and oral administration.

In a double-blind, placebo-controlled study, the effects of caroverine (CAS 23465-76-1, Spasmium)--a quinoxaline derived from isoquinoline, the basic structure of papaverine, originally developed as a spasmolytic drug which may, however, exert central effects due to an unspecific calcium channel blocking action and glutamate antagonism--were investigated utilizing EEG-mapping, psychometric and psychophysiological measures. Fifteen healthy volunteers (8 males and 7 females), aged 20-35 years, received randomized and at weekly intervals 40 and 80 mg caroverine intravenously, 40 and 80 mg caroverine orally, as well as placebo. EEG recordings, psychometric and psychophysiological tests, as well as evaluation of pulse, blood pressure and side-effects were carried out at 0, 1, 2, 4, 6 and 8 h. Multivariate analysis of EEG mapping data demonstrated that caroverine exerted a significant action on human brain function, as compared with placebo, at all given dosages, as early as in the 1st and as late as in the 8th hour after both intravenous and oral administration during resting (R-EEG) and vigilance-controlled recording (V-EEG). Subsequent univariate analyses revealed, however, differential effects of caroverine--dependent on recording conditions and doses. In the resting condition, an increase of absolute and relative delta and theta power, a decrease of alpha and beta power and a slowing of the centroid of the delta and theta activity occurred, reflecting sedative action. The latter was slightly time- and dose-dependent (more sedation in earlier hours after higher doses). However, in the vigilance-controlled EEG, a dose-dependent decrease of delta and theta power, an increase of alpha power and an acceleration of the centroid of the delta and theta suggested vigilance-promoting effects, which were more pronounced in the later than earlier hours. Psychometric investigations confirmed these differential central effects. In regard to the noopsyche, an improvement was noted 6 h after the lowest oral dose. In the thymopsyche, a deterioration occurred after all doses except the highest oral dose, suggesting sedation. The latter was also seen after all active compounds as a trend in psychophysiological variables. The drug was well tolerated.

Administration, Oral↗

PubMed1994

Discrimination between demented patients and normals based on topographic EEG slow wave activity: comparison between z statistics, discriminant analysis and artificial neural network classifiers.

The topographic distributions of absolute delta and theta powers were used to classify demented patients and normals by means of z statistics, discriminant analysis and artificial neural networks (NN). The data were taken from two psychopharmacological studies in mildly to moderately demented patients (111 and 96 patients for studies I and II, respectively) and from 56 normal healthy controls. All patients were diagnosed according to DSM-III criteria and were free of medication for at least 2 weeks. The NN used was a strictly layered feed-forward network with complete connections. The z-transformed absolute power values in the combined delta and theta frequency range at 17 electrodes, recorded in a 3 min vigilance-controlled EEG with eyes closed, were used as input. After having trained the NN successfully by backpropagating of errors, the generalization test with independent data results in a classification performance of 90% determined by "relative operating characteristic" analysis. The NN out-performed z statistics and discriminant analysis. This high percentage of correct classifications may justify the development of further application of NNs based on topographic EEG data.

Aged↗

PubMed1994

BMS-181168 for protection of the human brain against hypoxia: double-blind, placebo-controlled EEG mapping studies.

In a double-blind, placebo-controlled, cross-over trial, the antihypoxidotic properties of BMS-181168 (previously BMY 21502)--a 1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2- pyrrolidinone alleviating impairment of learning and memory in the animal--were studied utilizing EEG mapping under an experimental hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at 6000 m altitude), which was inhaled for 23 minutes under normobaric conditions by 16 healthy male volunteers (aged 23-35 years, mean 27.2 years). After an adaptation session, they received in randomized order at weekly intervals oral single doses of placebo, or of 100 mg, 200 mg, and 400 mg BMS-181168. Evaluation of blood gases (PO2, PCO2, SO2), adverse events, and EEG mapping was carried out prior to drug administration and 2, 4, 6 and 8 hours post-drug, on each occasion under normoxic and transient hypoxic conditions. Hypoxemia was controlled by drawing arterialized capillary blood samples from the earlobes after hyperemization of the latter (after 0, 14, and 23 minutes of hypoxic gas inhalation) and by oximetry. After 23 minutes of inhalation, analysis showed a drop in PO2 from 98 to 48 mm Hg, in PCO2 from 41 to 31 mm Hg, and in SO2 from 97 to 80%. Descriptive statistical analyses of EEG mapping data demonstrated under hypoxia/placebo conditions an increase in delta/theta activity and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an increase in the alpha and beta centroid, which suggests a marked deterioration in physiological vigilance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Pharmacokinetic and -dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and 0.4 mg suriclone as well as 1 mg alprazolam as reference compound. Investigations were carried out before and 1, 2, 4, 6 and 8 h after drug administration. 3. Pharmacokinetic investigations by radioimmunoassay showed a dose-dependent fast rise of plasma concentrations with a peak at 1 h and a rapid decline thereafter. Both the Cmax and the AUC values exhibited a linear relationship to dose. 4. EEG brain mapping demonstrated significant CNS effects of both compounds, characteristic for tranquillizers (increase of beta, decrease of alpha and increase of delta activity; attenuation of total power and acceleration of the centroid, i.e. centre of gravity frequency). When compared with alprazolam, suriclone exerted less sedative effects. 5. Time-efficacy calculations showed the pharmacodynamic peak effect of suriclone from the 2nd to the 4th hour, and of alprazolam in the 1st hour. Dose-efficacy calculations showed that the most pronounced CNS changes occurred after 1 mg alprazolam, followed by 0.4, 0.2 and 0.1 mg suriclone. 6. Psychometric investigations demonstrated no significant effects after the two lower doses of suriclone, while 0.4 mg and 1 mg alprazolam induced a decrement both in noopsychic and thymopsychic variables seen after higher doses of anxiolytic sedatives. Psychophysiology (critical flicker fusion, pupillometry, and skin conductance measures) pulse rate, systolic and diastolic blood pressure remained unchanged. 7. Psychophysiology (critical flicker fusion, pupillometry and skin conductance measures) showed differential dose-dependent effects. Pulse rate, systolic and diastolic blood pressure remained unchanged. Anxiolytic-characteristic side-effects (tiredness, drowsiness, etc.) occurred predominantly after the highest doses 0.4 mg suriclone and 1 mg alprazolam.

Administration, Oral↗

PubMed1994

Insomnia in generalized anxiety disorder: polysomnographic, psychometric and clinical investigations before, during and after therapy with a long- versus a short-half-life benzodiazepine (quazepam versus triazolam).

Within a double-blind, comparative study on the effects of the long-half-life benzodiazepine (BDZ), quazepam, and the short-half-life BDZ, triazolam, on clinical symptomatology, sleep and anxiety of 45 patients with insomnia based on a mild to moderate generalized anxiety disorder (GAD) (ICD-9 code: 307.42-1, 300,0; ASDC-APSS-Code: A.2.a), we compared, in a first step at baseline, drug-free polysomnographic and psychometric data of 22 patients recorded in the laboratory (L-group) and 21 patients recorded by the Oxford Medilog 9000 system at home (H-group) with those of normal controls. Sleep efficiency, total sleep time, wake within total sleep period (middle insomnia) and wake before buzzer (late insomnia) were significantly deteriorated in both patient groups as compared with controls, while sleep induction time only differed significantly in home recordings. Regarding sleep architecture, stage (S)2 was reduced, S3 and S4 increased in the H-group only, while no intergroup differences were seen in S1, SREM and REM latency. Subjective sleep quality was reduced in both patient groups, but not awakening quality. Psychometric tests in the morning demonstrated for the noopsyche, only a significantly deteriorated psychomotor activity in both patient groups. In the thymopsyche, evening well-being and mood in the morning were reduced in both the L- and H-group, affectivity and morning well-being only in the H-group. The psychopharmacological part of the study was completed by 40 patients (there were 4 drop-outs in the triazolam, 1 in the quazepam group). They were treated after 1 week placebo with either 15-30 mg (median 15 mg) quazepam or 0.25-0.5 mg (median 0.25 mg) triazolam for 4 weeks, and thereafter for 2 weeks with placebo. Anxiety (rated by HAMA and SAS) improved significantly with both drugs and remained improved throughout 2 weeks post-drug placebo, with quazepam being slightly superior to triazolam. Polysomnography demonstrated a shortened sleep onset only after quazepam. Sleep efficiency improved after acute administration of both drugs, but the improvement was maintained by quazepam only (tolerance development with triazolam). Rebound insomnia was observed only in the 1st post-triazolam placebo night (significant intergroup difference based on confirmatory testing). S2 increased, S3 + S4 decreased under and after quazepam, which represents a normalization in home-recorded GAD patients. S1 decreased with both drugs, SREM only under quazepam. Subjective sleep quality behaved very similarly to objective sleep efficiency. Awakening quality improved after acute therapy with both drugs, somatic complaints only with quazepam.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗