PubMed Health⌕ Search

Biomedical subjects

L Linzmayer

Publications and source records attributed to L Linzmayer.

At least 91 records · Page 5Linked to original sources
PubMed1982

Objective measures in determining the central effectiveness of a new antihypoxidotic SL-76188: pharmaco-EEG, psychometric and pharmacokinetic analyses in the elderly.

In a double-blind, placebo-controlled, cross-over study, the blood levels as well as the encephalotropic and psychotropic properties of SL-76188 - a new molecule of the hexahydrocanthinone series - were studied in 10 elderly subjects by means of quantitative EEG and psychometric analysis. They received randomized and in weekly intervals single oral doses of 100, 175 and 250 mg SL-76188, placebo and 20 mg D-amphetamine as the reference substance. Blood sampling, EEG recordings and the monitoring of blood pressure, heart rate and side effects were done at 0, 1, 2, 4, 6 and 8 h. Psychometric tests were performed at 0, 2, 4, 6 and 8 h. HPLC demonstrated that the drug was rapidly absorbed as the peak plasma levels were found within the first 2 h. A dose-dependent kinetic profile was observed based on exponential correlations between dose and peak plasma levels and AUC. Computer-assisted spectral analysis of the EEG showed a significant CNS effect as compared with placebo. The attenuation of delta and theta activity, increase of alpha and certain beta activities and the acceleration of dominant frequency suggested an improvement in vigilance. This was reflected behaviorally by an improvement in concentration, attention variability, complex reaction and mood, especially in the higher dosage range. The reference substance 20 mg D-amphetamine exhibited more psychostimulatory properties, which were also observed in regard to the side effects. Blood pressure and heart rate increased only with D-amphetamine as compared to placebo. Finally, the relationship between kinetic and dynamic data was explored. An increase in pharmacodynamic changes on the descending slope of the kinetic curve resulted in a so-called 'hysteresis loop', the implication of which is discussed.

Aged↗
PubMed1982

The pharmacokinetics of nomifensine. Comparison of pharmacokinetics and pharmacodynamics using computer pharmaco-EEG.

Pharmacokinetics and pharmacodynamics of nomifensine infusions as compared with oral preparations were investigated in a double-blind place-controlled crossover study in 10 healthy normal volunteers. They received randomized in weekly intervals 75 mg nomifensine and placebo intravenously as well as placebo, 75 and 150 mg nomifensine orally. Blood samples, quantitative EEG evaluations, psychometric tests, blood pressure, pulse rate and side effects were obtained and monitored at the hours 0, 1, 2, 4, 6 and 8. Nomifensine serum levels were determined by a radioimmunoassay; peak levels occurred within the first 2 h, the elimination half-life was around 2 h, both results indicating fast absorption and elimination. While the evaluation of the total nomifensine demonstrated almost identical bioavailability of the oral and intravenous form, free nomifensine levels after 75 mg i.v. were more similar to those after 150 mg than 75 mg p.o. Digital computer period analysis of the EEG confirmed nomifensine as a drug with a significant effect on the CNS as compared with placebo, showing in fact an antidepressant 'pharmaco-EEG profile' similar to desipramine. Evaluation of dose-effect curves demonstrated that 75 mg i.v. was the most effective drug, being closer to 150 than 75 mg p.o. The latter oral dosage could be discriminated from placebo only in certain variables at certain times. Concerning time-effect, nomifensine was most effective around the 6th hour post-drug, which was similar to the psychometric findings, thus showing a considerable delay compared to the peak serum concentration. Relating pharmacodynamic findings to pharmacokinetic results it became evident that free nomifensine may be of far greater importance for the drugs encephalotropic and psychotropic properties than the total unconjugated and conjugated nomifensine--thus justifying the development of a parenteral preparation. Finally, the relationship of blood levels and CNS effects was found to have a characteristic 'hysteresis loop' shape suggesting a delay of pharmacodynamic effects as opposed to the serum concentrations. This delay may be due to a slowly formed active metabolite, the drug acting on deep compartment receptors or both.

Adult↗
PubMed1981

[Contribution to the objective evaluation of the personality features of the colitis patient (author's transl)].

Before becoming in-patients in the psychosomatic department 26 patients (male and female) with ulcerative colitis were subjected to a series of personality tests (MMPI, FPI, GT, EPI) and compared with a normal control group. According to these tests and in psychopathological aspects the colitis patients deviated from the normal control group. The colitis patients showed more anxiousness and neuroticism and a tendency to introversion. The psychological results established by the tests and the psychopathological findings coincided especially in respect to the depressiveness. In connection with the inhibited depressiveness the question arises, whether the aggressive modalities, which can be substantiated by internal aspects but not optimally by the tests, can be objectively evaluated.

Adolescent↗
PubMed1980

Classification and assessment of cerebral bioavailability of lopirazepam (D-12524) by quantitative EEG and psychometric analysis.

In this double-blind, placebo-controlled study the CNS efficacy and pharmacodynamic properties of 3-hydroxy-5-(o-chlorophenyl)-7-chloro-1,2-dihydro-3H-pyrido[3,2-e]-1,4-diazepin-2-one (lopirazepam, D-12524) was investigated in a group of 10 normal volunteers. Quantitative EEG and psychometric analyses and clinical evaluations were done before as well as 2, 4, 6 and 8 h after oral administration of single doses of placebo, 3 mg, 5 mg and 10 mg lopirazepam and 10 mg prazepam. EEG digital computer period analysis demonstrated dose-dependent changes which are typical of the class of anxiolytics and which started in the 2nd hour, peaked in the 4th hour and lasted after 3 mg, 5 mg and 10 mg up to the 4th, 6th and 8th hour, respectively, 10 mg D-12524 produced an additional augmentation of slow waves indicating sleep-inducing qualities in this dosage. The equipotent dosage to 10 mg prazepam seems to be 5 mg. Psychometric analyses demonstrated an improvement in attention, psychomotor performance, mood and affectivity after 3 mg, opposite changes after 10 mg D-12524. Flickerlight fusion, reaction time, after-image and EAS score were determined as well. Data concerning side effects, pulse rate and blood pressure suggested a good tolerance of the drug.

Adult↗
PubMed1980

Quantitative EEG and psychometric analyses in assessing CNS-activity of Ro 13-5057--a cerebral insufficiency improver.

In a double-blind, placebo-controlled cross-over study, the encephalotropic, psychotropic and pharmacodynamic properties of Ro 13-5057/001, a new 2-pyrrolidinone derivative, were investigated in 10 geriatric subjects. They received in randomized order at weekly intervals, single oral doses of placebo, 250 mg, 500 mg and 1000 mg Ro 13-5057, as well as 2000 mg pirazetam as reference drug. EEG recordings, psychometric testing and evaluation of blood pressure, pulse rate and side effects were carried out at the hours 0, 2, 4, 6, 8 and 24. Power spectral density analysis of the EEG demonstrated Ro 13-5057 to be an encephalotropic drug, as statistically significant CNS changes occurred in comparison to placebo, which were characterized by a decrease of delta activity, increase of alpha activity and slow beta activity and acceleration of dominant frequency. The reference drug 2000 mg pirazetam induced similar changes. Such alterations were previously described by us as typical for certain antihypoxidotic/nootropic drugs and are indicative of improvement in vigilance. Psychometric data confirmed this interpretation of neurophysiological alterations as shortening of reaction time, acceleration of tapping speed, CNS activation as measured by the Archimedean spiral, improvement in mood as well as improvement in qualitative but deterioration of quantitative aspects of attention were observed at various times after the active substances as compared with placebo. Regarding time-efficacy, the peak effect in CNS changes was noted in the 2nd hour after Ro 13-5057, but interestingly there were also alterations as late as 24 hours after oral administration. Dose-efficacy curves suggested 1000 mg Ro 13-5057 as the most effective compound of the study. The lack of side effects and clinically relevant changes in blood pressure and pulse rate indicates that the drug is well tolerated in man.

Aged↗
PubMed1977

Classification and determination of cerebral biovailability of psychotropic drugs by quantitative "pharmaco-EEG" and psychometric investigations (studies with AX-A411-BS).

Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed.

Adult↗
PubMedDate not supplied

Amantadine infusions in mild dementia: acute double-blind placebo-controlled EEG mapping and psychometric studies.

In a double-blind, placebo-controlled study, the acute central effects of amantadine infusions (200 mg for 1 h) were studied in 20 mildly demented patients (DSM-III-R) utilizing EEG mapping as well as psychometry and psychophysiology at the hours 0, 2, 4, 6 and 8. Multivariate analysis of the EEG demonstrated a significant CNS effect of 200 mg amantadine as compared with placebo mostly at the 4th and 6th hour. These effects were primarily over temporo-occipital, fronto-temporal and temporal regions. Univariate analysis showed a decrease of total power and of absolute power in all frequency bands. Furthermore, an increase of relative delta and beta activities, a decrease of theta and alpha activities, as well as an acceleration of the respective centroids of the alpha, beta and total activity were observed. The delta/theta centroid showed initially a slight increase and thereafter a clear decrease. The changes were similar to those seen after psychostimulants. Multivariate analysis of noopsychic variables showed an improvement in the 6th hour after amantadine and no changes after placebo, but inter-drug differences did not reach significance. Univariate analyses revealed differential results which included improvement in digit span and deterioration in the speed related test such as DSST and reaction time. In thymopsychic variables, de-activation was observed after amantadine as compared with placebo in the 2nd to the 6th hour with a maximum in the 4th hour. As patients felt themselves slightly over-activated before treatment, de-activation may be regarded as improvement of vigilance in the narrow sense of the word. There were no psychophysiological changes.

Clinical Trial↗
PubMedDate not supplied

Effect-kinetics on brain protection of two codergocrine-mesylate preparations (Aramexe retard and Hydergine) by EEG mapping and psychometry under hypoxia.

In a double-blind, placebo-controlled study the effect-kinetics on brain protection of a new retard formulation of codergocrine-mesylate (CDM) (Aramexe retard, 5 mg) were investigated and compared with a standard CDM drug (5 mg Hydergine) utilizing blood gas analysis, EEG mapping and psychometry. A transient, reversible hypoxic hypoxidosis (i.e. impairment of cerebral metabolism due to hypoxia) was experimentally induced by a fixed gas combination of 9.8% oxygen (O(2)) and 90.2% nitrogen (N(2)) (found at an altitude of 6000 m), which was inhaled for 23 min under normobaric conditions by 18 healthy volunteers. After an adaptation session they received randomized 5 mg Aramexe retard, 5 mg Hydergine and placebo. Evaluation of blood gases, EEG mapping and psychometry was carried out at 0,2, 4,6, and 8 h after oral drug administration - each time under normoxic and hypoxic conditions. Blood gas analysis demonstrated a drop in SaO(2) from 99% under normoxia to 70% under hypoxia, in Po(2) from 100 to 33 mmHg, and in Pco(2) from 36 to 31 mmHg, while pH increased from 7.43 to 7.48. Base excess and standard bicarbonate remained stable. Under hypoxia EEG mapping exhibited an increase in delta/theta, a decrease of alpha and increase of beta activity, as well as a slowing of the centroid of the total power spectrum, which reflects deterioration of vigilance. Both CDM preparations significantly attenuated this vigilance decrement, with 5 mg Hydergine showing its encephalotropic peak effect in the second hour, 5 mg Aramexe retard in the sixth and eighth hours. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noo- and thymopsyche (by 53% under placebo), which was significantly mitigated by both 5 mg Aramexe retard (19%) and Hydergine (32%).

Clinical Trial↗
PubMedDate not supplied

Psychophysiological diagnostics in alcohol dependency: Fourier analysis of pupillary oscillations and the receptor test for determination of cholinergic deficiency.

Mnestic disturbances in alcoholics may be related to cholinergic deficiency as well as to central nervous system inactivation. After instillation of tropicamide, cholinergic receptors are blocked and pupillary dilatation occurs. It is assumed that the more severe the cognitive deterioration, the wider the pupillary dilatation. Pupillary oscillations reflect central activation. Changes of pupillary diameter after topical instillation of tropicamide and pupillary oscillations were measured in 44 alcohol-dependent patients aged 40-55 years, diagnosed according to the DSM-III-R as severe alcoholics (>7 symptoms), having been abstinent for at least 3 weeks (objectively tested with carbohydrate-deficient transferrin), compared with 18 healthy controls. The pupillary diameter of the left eye was measured eight times within 103 min, as were pupillary oscillations. Using Fourier analysis, the amplitudes of oscillations were measured in five frequency bands and the sum of the frequency bands was calculated. In addition, central activation was measured during a calculation test at 3 and 103 min. The pupillary dilatation of 22% in alcoholics compared to 14% of normal controls after tropicamide raises the question of a cholinergic deficit in alcohol dependence. With regard to basic activation, measured by Fourier analysis of pupillary oscillations, alcoholics demonstrated significantly lower power (sum of the frequency bands) than controls at baseline and at 3, 20, and 40 min (P < 0.01) as well as at 60, 80, 100, and 103 min (P < 0.05). After a cognitive task, a difference between alcoholics and healthy controls was found at 3 min. Alcoholics showed lower basic activation and decreased cognitive activation. By means of cross-validation, a differentiation between alcohol-dependent patients (n = 44 and n = 42 respectively) and normal controls (n = 18) was possible.

Adult↗
PubMedDate not supplied

Memory deficits in patients with DSM-IV obsessive-compulsive disorder.

Neuropsychological testing provides increasing evidence that certain memory deficits might play an essential role in the emergence of doubts and, as a result, in perpetuating checkers' rituals. Another account of doubting implicates meta-cognitive factors, such as confidence in memory. The present study examined mnestic functioning and self-perception of memory ability in a group of 27 nondepressed patients with obsessive-compulsive disorder (OCD) and 27 normal controls. All patients met DSM-IV and ICD-10 criteria for OCD, displayed prominent behavioral checking rituals and had to show a score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of at least 16. Significant deficits in intermediate (Lern- und Gedächtnistest; LGT-3) and immediate (Corsi Block-Tapping Test) nonverbal memory were identified in the patients with OCD compared to normal controls. Contrary to predictions, OCD patients also showed a significant deficit in general memory and verbal memory (LGT-3). With respect to meta-cognition, OCD patients reported less confidence in their memories than controls. These findings suggest that obsessional doubt reflects a deficit in memory as well as a deficit in memory confidence. Depending on which dysfunction predominates, different therapeutic procedures seem to be required.

Adolescent↗
PubMedDate not supplied

EEG brain mapping and psychometry in age-associated memory impairment after acute and 2-week infusions with the hemoderivative Actovegin: double-blind, placebo-controlled trials.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic effects of Actovegin--a protein-free metabolically active hemoderivative improving oxygen and glucose utilization--were investigated in age-associated memory impairment (AAMI) patients, utilizing EEG brain mapping, psychometric and psychophysiological analyses. Each patient had a treatment of 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily with an interval of 3 weeks in between (the order of drugs sequence was randomized). Pharmacodynamic evaluations were carried out 0, 2, 4, 6 and 8 h after the administration of one single infusion on day 1 (acute effect), at 0 h on day 15 (subacute effect) as well as 2, 4, 6 and 8 h after one additional superimposed infusion on day 15 (superimposed effect). EEG brain mapping demonstrated that Actovegin exerted a significant action on the human brain function as compared with placebo characterized by a decrease of delta and theta, an increase of alpha-adjacent slow beta, a decrease of fast beta, an acceleration of the centroid of the delta/theta and alpha activity, a slowing of the beta centroid and an increase of the centroid of the total activity. Topographically the encephalotropic effects were mostly pronounced in the parietal, frontocentral and temporooccipital regions. These changes are indicative of an improvement of vigilance which was proven also by psychometric investigations at the behavioral level. Actovegin improved the noopsyche mostly in regard to attention, memory and rigidity/perseveration measures. In regard to the thymopsyche an improvement was noted in mood, affectivity, well-being and sedation. Psychophysiological evaluations demonstrated an increase in CFF, skin conductance, pupillary diameter and shortening of the latency and augmentation of the amplitude of the pupillary response. Time-efficacy calculations exhibited more effect after subacute than acute administration with the pharmacodynamic maximum in the 4th h after the superimposed dose. Evaluations of pulse, blood pressure and side effects demonstrated a very good tolerability of the drug. Our present neurophysiological, psychometric and psychophysiological findings confirm earlier results obtained in elderlies with similar methodology.

Aged↗
PubMedDate not supplied

[Functional improvement of the aging brain: placebo controlled pharmaco-EEG and psychometric studies with a metabolically active hemoderivative (Actovegin)].

A double-blind, placebo-controlled pharmaco-EEG and psychometric study was carried out to investigate the encephalotropic and psychotropic properties of a metabolically active hemoderivate (Actovegin) in 10 elderly subjects with a mean age of 65 years, and to form hypotheses about its therapeutic efficacy. They received randomized and in weekly intervals single oral doses of 6 dragées (drg.) Actovegin, 9 drg. Actovegin as well as placebo. Computer-assisted spectral analysis of the EEG demonstrated an increase of alpha- and beta-activities, an acceleration of the alpha-centroid as well as of the centroid of the total activity after Actovegin as compared with placebo, while slow activities tended to decrease--specifically in the 4th and 6th hour. These neurophysiological alterations indicate an improvement in vigilance of the elderly subjects, which was reflected in the psychometric tests. The latter demonstrated in the multivariate analysis a significant superiority of Actovegin over placebo. Actovegin induced--especially after 6 drg.--an increase in critical flicker frequency, prolongation of the after-effect as evaluated by means of the Archimedean spiral, shortening of reaction time as well as cognitive improvement in the Pauli-Test. In the autonomic nervous system, the widening of the pupillary diameter and the increase in skin conductance suggested also an activation at the ANS level. Our controlled investigations demonstrate that Actovegin--even after oral administration--may produce neurophysiological and clinical effects.

Aged↗