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Biomedical subjects

L Linzmayer

Publications and source records attributed to L Linzmayer.

At least 73 records · Page 4Linked to original sources
PubMed1986

Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of acutely and chronically administered milacemide--a new derivative of glycine showing anti-convulsant action by increasing GABA concentrations and endogenous glycine pools in the brain--were investigated in 12 elderly subjects in their late sixties. Each subject had a treatment period of 2 weeks (with 400 mg b.i.d. and 1,200 mg b.i.d. orally administered in week 1 and 2, respectively) and another period of 2 weeks with placebo. A treatment-free interval of 1 week was introduced in between. EEG-recordings, psychometric and psychophysiological tests as well as evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 2, 4, 6 and 8 after the administration of one single dose of 400 mg or placebo (acute effect), after 1 week's and 2 weeks' chronic administration (chronic effect), as well as after one additional superimposed dosage of 400 mg and 1,200 mg on days 8 and 15 of chronic treatment, respectively (super-imposed effect). Computer-assisted spectral analysis of the EEG demonstrated after single doses of 400 mg milacemide significant changes in the resting EEG indicative of improvement in vigilance (beta augmentation, acceleration of the beta centroid), while in the vigilance-controlled recording condition a dissociative vigilance shift occurred seen also after antidepressants of the amitriptyline and imipramine type (increase of both delta/theta and beta activity, decrease of alpha activity). One week chronic treatment resulted in the same V- and R-EEG profiles. However, after the 2nd weeks' treatment with higher doses as well as after one additional superimposed dosage of 1,200 mg milacemide both V- and R-EEG recordings demonstrated dissociative vigilance shifts. Time/treatment-efficacy calculations showed the chronic effect to be more pronounced than the acute effect, which peaked in the 2nd hour after oral drug administration. Psychometric analyses exhibited in noopsychic variables a significant improvement in intellectual and mnestic performance but even more so in the thymopsyche an improvement in subjective well-being and affectivity. Psychophysiological tests showed a decrease in CFF, while static and dynamic pupillometry and skin conductance measures remained unchanged. Pulse rate, systolic and diastolic blood pressure were not altered. The findings are discussed in the light of the involvement of GABA in the pathogenesis and treatment of affective disorders.

Acetamides↗
PubMed1986

Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor.

This study is concerned with the alterations in central and peripheral psychophysiological measures and psychometric variables after experimental manipulation of the most important inhibitory transmitter system of the CNS, the gamma-aminobutyric acid (GABA) system. Vigabatrin (GVG), a new enzyme-activated, irreversible inhibitor of GABA transaminase, which increases cerebrospinal fluid concentrations of GABA and other substrates of GABA transaminase, was given in single oral doses of 1 g, 2 g and 3 g to 10 normal healthy volunteers. In this double-blind, placebo-controlled crossover study, 3 mg lorazepam was given as reference compound. Blood sampling for vigabatrin kinetics, EEG recordings and evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6, 8 and 24, and psychometric tests at the same times (except the first hour). Pharmacokinetic analyses demonstrated good absorption of GVG with peak plasma concentrations found within the first two hours, dose-dependent areas under the plasma concentration-time curves and about 65% recovery in the 24-h urine. Computer-assisted spectral analysis of the EEG suggested that GVG produces only small changes in the normal CNS, characterized by an augmentation of total power, absolute and relative power of the beta activity and acceleration of the centroid of the total activity. There was also a trend towards an increase of alpha activity and of the absolute and relative power of the dominant frequency, decrease in the alpha centroid and increase of the centroid of the combined delta and theta activity. Lorazepam 3 mg, in contrast, produced highly significant changes characterized by a decrease of total power, alpha activity, absolute and relative power of the dominant frequency and centroid of the combined delta and theta activity, while beta activity as well as the centroid of the alpha, beta and total activity increased. In the resting condition an additional augmentation of slow activity suggested hypnotic properties of 3 mg lorazepam. The latter changes are typical for anxiolytic sedatives and were also reflected at the behavioral level where psychometric data demonstrated a deterioration in the noo- and thymopsychic parameters and sedative effects in psychophysiological variables. GVG, on the other hand, produced only subtle changes characterized by an improvement of noo- and thymopsychic variables and vegetative activation.

4-Aminobutyrate Transaminase↗
PubMed1986

Pharmacokinetic and dynamic studies with a new anxiolytic imidazo-pyridine alpidem utilizing pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the pharmacokinetic and pharmacodynamic effects of a new imidazo-pyridine derivative, alpidem (SL80.0342) and the 1,4 benzodiazepine lorazepam were investigated utilizing quantitative EEG and psychometric testing. Ten normal volunteers received randomized (latin square) single oral doses of placebo, 25 mg, 50 mg and 100 mg alpidem and 2.5 mg lorazepam at weekly intervals. Blood level sampling, EEG recordings, evaluation of pulse, blood pressure and side-effects were carried out at 0, 1, 2, 4, 6 and 8 hours post drug; psychometric and psychophysiological investigations at the same time periods except for the first hour. Computer-assisted spectral-analysis of the EEG demonstrated an anxiolytic profile after both compounds, characterized by an increase of beta activity, decrease of alpha activity and acceleration of the centroid of the total activity and total beta activity. Total power was attenuated, delta activity augmented and the centroid of the combined delta and theta activities decreased. The latter changes were most pronounced after 2.5 mg lorazepam suggesting it is more sedative than alpidem. Dose/treatment efficacy calculations revealed 2.5 mg lorazepam as the most CNS-active compound, followed by 100 mg, 50 mg and 25 mg alpidem. Based on a multivariate analysis 2.5 mg lorazepam could be differentiated from placebo at all times, 100 mg alpidem in the first, second and fourth hours, 50 mg only in the second hour. Time-efficacy calculations showed a marked CNS effect after alpidem in the first hour with a peak in the second hour, a gentle decline to the fourth hour and thereafter a rapid decline up to the eighth hour. In contrast, 2.5 mg lorazepam showed a slower rise in CNS activity which peaked in the fourth hour and declined slowly thereafter. These pharmacodynamic effects paralleled the blood level course of both compounds, as well as the time-course of psychometric changes. The latter were characterized by a deterioration in psychometer function after 2.5 mg lorazepam, which was less pronounced after 100 mg alpidem, while 50 mg and 25 mg showed no significant difference from placebo. Subjective ratings of mood showed a decrement which was most pronounced after 100 mg alpidem, less so after 50 mg, with no difference from placebo after 25 mg or lorazepam. Finally, there were no significant inter-drug differences with regard to psychophysiological variables.

Adult↗
PubMed1986

Evaluation of encephalotropic and psychotropic properties of gabapentin in man by pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of gabapentin - a new gaba-analogue with anticonvulsant and antispastic properties penetrating the blood brain barrier easily - were studied in 10 normal subjects by means of quantitative pharmaco-EEG and psychometric analyses. They received randomized and in weekly intervals single oral doses of 50 mg, 100 mg, 200 mg and 400 mg gabapentin as well as placebo. EEG recordings and evaluation of pulse, blood pressure and side effects were carried out after 0, 1, 2, 4, 6 and 8 hours; psychometric tests were done at the same times except for the first hour. Computer-assisted spectral analysis of the EEG showed moderate though significant central effects of gabapentine in doses of 200-400 mg as compared with placebo, which were maximally pronounced in the 2nd hour post drug. These alterations were generally characterized by an attenuation of total power, augmentation of delta and theta activity and a decrease of alpha activity indicating CNS-inhibitory properties. Only at the late hours did the type of changes shift towards a vigilance-promoting one. Beta activity showed alternating changes. Psychometric and psychophysiological evaluations demonstrated subtle psychotropic effects as compared with placebo characterized mostly by an improvement in concentration, numerical memory, complex reaction and performance in the alphabetical reaction test while performance variability increased as well. Subjectively experienced well-being changed dose-dependently. CFF decreased after 100 mg as did pupil size after 50-200 mg. Evaluation of pulse, blood pressure and side effects demonstrated good tolerability of the drug.

Acetates↗
PubMed1986

Early clinical pharmacological trials with a novel partial benzodiazepine agonist/antagonist Ro 17-1812 using pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of a new partial benzodiazepine agonist Ro 17-1812 were investigated as compared to the pure agonist diazepam utilizing quantitative EEG and psychometric analysis as well as clinical observations. Ten normal volunteers received randomized (latin square) and at weekly intervals single oral doses of placebo, 0.05 mg, 0.1 mg and 0.2 mg Ro 17-1812 and 10 mg diazepam as reference drug. EEG recordings, psychometric tests and evaluation of pulse, blood pressure and side effects were carried out at the hours 0,1,2,3,4, and 6. Computer-assisted spectral-analysis of the EEG demonstrated after 10 mg diazepam a typical "anxiolytic" pharmaco-EEG profile characterized by an increase of beta activity, decrease of alpha activity and acceleration of the centroid of the total activity. Total power tended to decrease while delta activity tended to increase, although only in the resting condition. Ro 17-1812 induced in the vigilance controlled recordings a similar profile thereby exhibiting tranquilizing properties. However, in the resting condition the most consistent change was an increase of delta/theta activity along with a decrease of alpha activity, whereas only in the higher dosage range was beta activity also augmented. These data indicate a selective sedation after the novel partial agonist but are also reminiscent of changes seen after neuroleptic drugs. Dose/treatment efficacy calculations demonstrated 10 mg diazepam as the most CNS-effective drug followed closely by 0.2 mg Ro 17-1812, 0.1 and 0.05 mg while-placebo induced the least changes. Time-efficacy calculations showed a peak effect after 10 mg diazepam in the 1st hour with a gentle decline up to the 4th hour and thereafter again an increase (active metabolites), while the peak of Ro 17-1812 was consistently found in the 2nd hour with a steady decline thereafter as the encephalotropic effect in the 6th hour was less marked than in the 1st hour. Psychometric investigations showed the same time course of both compounds, with the most psychoactivity observed after 0.2 mg Ro 17-1812 and the least after placebo. The fact that the partial agonist induced more decrement in the noopsyche, but specifically in the thymopsyche, of the normal volunteers than the pure agonist may indicate a lower dependency risk of the former than the latter. Evaluation of pulse and blood pressure showed no clinically relevant findings.

Adult↗
PubMed1986

[Pupillometry in psychopharmacologic experiments].

Considering data of various clinical pharmacological studies, in which computer-assisted pupillometry was utilized, we investigated the following questions: What are the effects of drugs of 7 psychopharmacological classes on the human pupil? Do dose-efficacy and time-efficacy curves based on pupillary variables provide cues about pharmacodynamic properties of psychotropic substances? Is there a relationship between pupillometric and critical flicker frequency measures? Is there a relation between pupillometric and quantitative electroencephalographic changes? Are there correlations between static pupillometric and pharmacokinetic (e.g. blood levels) variables? Our investigations demonstrated that static pupillometry-utilized in the described manner and under certain experimental conditions - provide valuable information about effects of psychotropic drugs on the central and autonomous nervous system.

Adult↗
PubMed1985

[Computer-assisted static and light-evoked dynamic pupillometry in psychosomatic patients].

Microprocessor-assisted pupillometry was used in this psychophysiological study to investigate the pupillary diameter (static pupillometry) and visual-evoked pupillary reactions (dynamic pupillometry) in psychosomatic patients (duodenal ulcers, ulcerative colitis, cardiac phobia, anorexia nervosa, bronchial asthma) as compared with age-and sex-matched normal controls. Statistical analyses including multivariate methods demonstrated interesting differences between psychosomatic patients and normal controls, as well as between various subtypes of psychosomatic disorders and elucidated also the influence of a 6 weeks' course of psychotherapy. The data give valuable clues to symptom/syndrome-specific psychophysiological reaction types, which may be of considerable relevance for the characterization of psychosomatic diseases.

Adolescent↗
PubMed1985

Double-blind, placebo-controlled, clinical, psychometric and neurophysiological investigations with oxiracetam in the organic brain syndrome of late life.

The therapeutic efficacy and safety of oxiracetam (ISF 2522), a new nootropic cyclic GABA derivative, were investigated in a double-blind, placebo-controlled study in 40 patients with organic brain syndrome in late life. The psychopathology was characterized by memory deficits, intellectual dysfunction, lack of drive, and disturbance of affectivity. Patients were randomly assigned to a 4-week treatment with either 2 X 400 mg oxiracetam capsules t.i.d. or identical placebo capsules in the same dosing schedule. Evaluation of the psychopathology and side effects was carried out at weeks 0, 1 and 4; laboratory tests (hematology, blood chemistry and urinalysis), a battery of psychometric tests and quantitative EEG investigations were done at weeks 0 and 4. In the oxiracetam group a slight but significant improvement in global symptomatology was observed within 1 week, with further improvement after 4 weeks. In the placebo group, an improvement was seen only in the 4th week. Evaluation of the detailed psychopathology by means of the Sandoz clinical assessment geriatric scale (SCAG) showed in the oxiracetam group significant improvements in loss of appetite and vertigo after 1 week and in short-term memory, anxiety, emotional lability, fatigue, loss of appetite and vertigo after 4 weeks. In contrast, not a single item improved significantly during placebo treatment. Although the differences in SCAG scores between the two groups failed to reach statistical significance, the overall trend towards improvement was significantly better in the oxiracetam group. The tolerability of the drug was good.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

[Duration of spiral after-effects in psychosomatic patients (a psychophysiologic study and analysis of data using multivariate procedures)].

In a psychophysiological study the spiral after-effect, as measured by means of the Archimedes spiral, was investigated in 182 patients with psychosomatic disorders including duodenal ulcers, ulcerative colitis, anorexia nervosa, asthma and heart neurosis and compared with the results obtained in a control group of healthy volunteers (n = 30). Using multivariate data analysis it was possible to divide the total group of psychosomatic patients into various different subgroups which parallelled the subdivision from the clinical point of view. Moreover, the objectivation of the influence of psychotherapy lasting for 6 weeks on the duration of the after-effect was shown by this technique. These results suggest that the determination of the duration of the spiral after-effect may be of value in clinical psychodiagnostics.

Adolescent↗
PubMed1984

[Clinical psychodiagnosis using psychophysiologic procedures].

The present paper presents several new psychophysiological test methods and measures, which have been developed by the authors for utilization in the field of psychopathology and psychopharmacology. The main advantage of these new techniques seems to lie in the fact, that control and evaluation procedures are microprocessor-assisted which ensures objectivity, reliability and validity. The multidimensionality, e.g. the possibility to concomitantly evaluate several variables at the same time, and the economics, e.g. the short time effort involved in completing the tests, are further advantages. By means of the newly developed techniques several sensitive measures may be obtained which are of great value in the diagnostic process as well as in the assessment of drug effects in clinical psychopharmacology.

Arousal↗
PubMed1984

Classification and determination of pharmacodynamics of a new antihypoxidotic drug, vinconate, by pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of both orally and intravenously administered doses of vinconate (OC 340)--a new vincamine analogue--were studied in 10 elderly subjects in their sixties by means of quantitative EEG and psychometric analyses. They received at weekly intervals randomized single oral doses of placebo, 40 mg, 80 mg and 160 mg vinconate orally as well as placebo and 30 mg vinconate intravenously. EEG recordings and the monitoring of blood pressure, heart rate and side effects were carried out at the hours 0, 1, 2, 4 and 6. Psychometric tests were performed at the hours 0, 2, 4 and 6. Computer-assisted spectral analysis of the EEG showed a significant CNS effect of vinconate as compared with placebo characterized by a decrease of delta activity, increase of alpha and specifically of alpha-adjacent slow beta activity as well as an acceleration of the centroid of the total activity. Such changes were described previously by us after several other antihypoxidotics and are indicative of improvement in vigilance in the sense of Head (Br. J. Psychol., 14, 125-147). The encephalotropic effect was most pronounced after 160 mg vinconate p.o. followed by 80 mg and 40 mg vinconate orally, which timewise could be observed best in the 6th hour after drug administration. Changes after the i.v. injection of vinconate peaked as early as the 2nd hour post-drug. Psychometric investigations demonstrated only small psychotropic effects, which rarely reached the level of statistical significance as compared with placebo. Generally, the orally administered vinconate induced a trend towards an improvement of psychomotor activity, complex reaction and cognitive function as well as a significant improvement in attention and concentration, while the von Zerssen score increased as compared with placebo. 30 mg vinconate i.v., however, induced an improvement in mood as well as a shortening of reaction time and activation in the after-effect as compared with placebo in addition to a trend towards improvement in psychomotor activity, complex reaction and Pauli test. Evaluation of pulse rate, blood pressure and side effects showed a good tolerance of the drug. The findings are discussed.

Aged↗
PubMed1984

Encephalotropic and psychotropic effects of intravenous buflomedil in the elderly: double-blind, placebo-controlled pharmaco-EEG and psychometric studies.

In a double-blind placebo-controlled study, the encephalotropic and psychotropic properties of intravenously administered buflomedil--a new vasoactive drug--were studied in 10 elderly volunteers in their 60s by means of quantitative EEG and psychometric analyses. At weekly intervals the patients received randomized (latin square design), single, intravenous doses of placebo, 50 mg, 100 mg and 200 mg buflomedil as well as 2000 mg piracetam as reference substance. EEG recordings and the monitoring of blood pressure, heart rate and side-effects were carried out at hours 0, 1, 2, 4, 6 and 8. Psychometric tests were performed at hours 0, 2, 4, 6 and 8. Computer-assisted spectral analysis of the EEG demonstrated that buflomedil exerted a significant effect on the central nervous system (CNS) as compared with placebo, characterized by a decrease of delta and theta, increase of alpha and alpha-adjacent beta activity as well as by an acceleration of the centroid of the alpha activity and also of the total activity. 2 g piracetam induced the same type of changes only at the end of the recording day. These quantitative EEG changes have been previously observed after several antihypoxidotic/nootropic drugs and indicate an improvement in vigilance in the sense of Head. Treatment-efficacy calculations demonstrated that 200 mg buflomedil was the most CNS-effective substance followed by 100 mg and 50 mg buflomedil and 2 g piracetam. Time-efficacy calculations showed that the encephalotropic effects were already marked in the 1st hour after i.v. application, decreased to a low in the 4th hour and subsequently increased again to reach a maximum in the 8th hour. In contrast, 2 g piracetam induced CNS changes which increased from the 1st throughout the 6th hour to show only a slight decline thereafter. The hysteresis between pharmacodynamic and pharmacokinetic findings is discussed. Psychometric investigations demonstrated that after 50 mg buflomedil i.v. there was a significant improvement as compared with placebo in cognitive function based on the Pauli test as well as an increase in correct reactions in the alphabetical reaction test. Doses of 100 mg buflomedil also produced an improvement in the Pauli test, attenuated errors in the reaction time task, improved complex reaction on the Vinnese Determinationsgerät, increased CFF but also errors in the concentration test.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1983

[Classification and determination of the pharmacodynamics of a new tetracyclic antidepressive agent, pirlindol, using pharmaco-EEG and psychometry].

In a double-blind placebo-controlled study the encephalotropic and psychotropic properties of a new tetracyclic pyrazino-indole derivative were studied in 10 normal volunteers. They received, randomized at weekly intervals, single oral doses of placebo, 75 mg, 150 mg and 225 mg pirlindol, as well as 75 mg imipramine, 20 mg tranylcypromine and 150 mg nomifensine as reference drugs. Pharmaco-EEG, psychometric and physiological data were obtained at the hours 0, 1, 2, 4, 6 and 8 after oral administration. Digital computer period analysis of the EEG demonstrated moderate CNS effects with pirlindol as compared with placebo. Its pharmaco-EEG profile, especially after higher dosage (150 and 225 mg), was characterized by a decrease in delta and theta activity, an increase in alpha activity and a delta and theta activity, an increase in alpha activity and a decrease in beta activity, as well as by an attenuation of the average frequency and frequency deviation and a trend towards an augmentation of the amplitude and amplitude variability. This profile is typical for antidepressants of the desipramine type and was also observed in our present study after 150 mg nomifensine and (although less markedly) and 20 mg tranylcypromine. 75 mg pirlindol induced, however, changes characterized by a concomitant increase in slow and superimposed fast activities and by a decrease in alpha activity. These alterations were described previously as typical for antidepressants of the imipramine type, and were also noted after 75 mg imipramine in the present study. Time-efficacy calculations showed the maximal pharmacodynamic effect of pirlindol in the 4th to 6th hour, of 75 mg imipramine in the 2nd hour, of 20 mg tranylcypromine in the 4th hour and of 150 mg nomifensine in the 6th hour. Dose/treatment-efficacy calculations identified in the 1st and 2nd hour post drug 75 mg imipramine as the most CNS-effective drug, in the 4th and 6th hour 150 mg pirlindol and in the 8th hour 225 mg pirlindol. Psychometric investigations showed only slight changes after pirlindol, reaching only rarely the level of statistical significance (improvement in attention after 225 mg pirlindol, decrease in tapping after 75 and 150 mg pirlindol, as well as attenuation of the complex reaction after all 3 doses of pirlindol). Concentration, attention-variability, psychomotor activity, CFF, after effect (Archimedean spiral), reaction time, mood and affectivity were not significantly altered as compared with placebo. Pulse, systolic and diastolic blood pressure did not show any clinical relevant changes either.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

Quantitative pharmaco-EEG and performance after administration of brotizolam to healthy volunteers.

The activity of brotizolam (0.1, 0.3 and 0.5 mg) was studied in normal subjects using quantitative pharmaco-EEG, psychometric and clinical evaluation. Power spectral density analysis showed no changes after placebo, while brotizolam increased beta-activity, decreased alpha-activity and increased the average frequency (anxiolytic pharmaco-EEG profile). In addition, 0.3 and 0.5 mg brotizolam augmented delta-activity indicating hypnotic activity. The highest dose (0.5 mg) of brotizolam decreased attention, concentration, psychomotor performance and affectivity, and increased reaction time. The lower doses of brotizolam also caused a decrease in attention and concentration, but tended to improve psychomotor performance, shorten reaction time, and did not influence mood or affectivity. Brotizolam (0.1 mg) is the minimal effective psychoactive dose with a tranquillizing effect, while 0.5 mg and to some extent 0.3 mg induce a sedative effect and may be regarded as hypnotic doses.

Adult↗
PubMed1983

Determination of pharmacodynamics of the new neuroleptic zetidoline by neuroendocrinologic, pharmaco-EEG, and psychometric studies--Part I.

In a double-blind, placebo-controlled, crossover study, neuroendocrinologic, encephalotropic, and psychotropic effects of a new antidopaminergic compound zetidoline (DL 308) were investigated in ten healthy volunteers. In randomized sequences at weekly intervals they received single oral doses of placebo; 10, 20, and 40 mg zetidoline; and 2 mg haloperidol as positive control according to a Latin square design. Plasma sampling for prolactin levels, EEG recording, evaluation of blood pressure, pulse and side effects were carried out at 0, 1, 2, 4, 6, and 8 h. Psychometric tests were done at 0, 2, 4, 6, and 8 h. The prolactin response to zetidoline proved to be dose-dependent and peaked within the first 2 h, whereas after 2 mg haloperidol, prolactin levels increased only as late as in the 6th and 8th h. This time course was similar to the neurophysiologic and psychometric ones. Computer period analysis of the EEG demonstrated after 10, 20, and 40 mg zetidoline slight, marked, and moderate central nervous system (CNS) changes as compared with placebo, which were characterized by an increase of theta and also beta activity, decrease of alpha activity and average frequency (primary wave), and attenuation of the amplitude, indicating CNS-inhibitory effects. These inhibitory effects were more pronounced after the intermediate dosage. In the 6th and 8th h after the 10-mg dosage but also after the 40-mg dose some activating properties were observed, as indicated by the decrease in slow waves and increase in slow beta activity and average frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗