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Biomedical subjects

B Saletu

Publications and source records attributed to B Saletu.

At least 181 records · Page 10Linked to original sources
PubMed1984

Early clinical pharmacological trials with a new anti-epileptic, milacemide, using pharmaco-EEG and psychometry.

In a double-blind placebo-controlled study the encephalotropic and psychotropic properties of milacemide (CP 1552 S) - a new derivative of glycine showing anti-convulsant action by increasing GABA concentrations and endogenous glycine pools in the brain - were studied in 12 normal subjects by means of quantitative EEG and psychometric analyses. They received randomized in weekly intervals single oral doses of 400 mg, 800 mg and 1600 mg milacemide, placebo as well as 600 mg sodium valproate and 1600 mg piracetam as reference compounds. EEG recordings and monitoring of blood pressure, heart rate and side effects were done at the hours, 0, 1, 2, 4, 6 and 8. Psychometric tests were performed at the hours 0, 2, 4, 6 and 8. Computer-assisted spectral analysis of the EEG showed significant effects of milacemide on the central nervous system (CNS) as compared with placebo, characterized by an attenuation of the delta activity as well as by an acceleration of the centroid of the slow activity but also of the total activity after all 3 doses. In addition, we noted an increase of beta activity after 400 mg, an increase of alpha activity after 800 mg, as well as an increase of alpha activity but decrease of beta activity after 1600 mg. These alterations, also seen after 600 mg sodium valproate, are reminiscent of quantitative EEG changes described after anti-epileptic drugs used in the treatment of Petit mal or generalized non-convulsive epilepsy. Moreover, they are also indicative of improvement in "vigilance" in the sense of Head which was also seen at the behavioural level specifically after the lowest doses of milacemide, as psychometric test demonstrated an improvement in attention, concentration, psychomotor activity and after-effect (indicating CNS-activation) as measured by means of the Archimedean spiral. This beneficial influence on performance declined with increasing doses. Evaluation of pulse, blood pressure and side effects demonstrated good tolerance after all administered substances. The findings are discussed.

Acetamides↗
PubMed1984

The hypoxia model in human psychopharmacology: neurophysiological and psychometric studies with aniracetam i.v.

Changes in human brain function and mental performance under hypoxic hypoxidosis as well as after intravenous injection of aniracetam - a new potentially nootropic 2-pyrrolidinone derivative - were investigated in a double-blind placebo-controlled study utilizing computer-assisted spectral analysis of the EEG and psychometric tests. Hypoxic hypoxidosis was induced by a fixed gas combination of 11.2% O2 and 88.8% N2, which was inhaled under normobaric conditions by 10 male healthy volunteers. The following substances were injected intravenously at weekly intervals according to a latin square design: placebo, 10 mg and 100 mg aniracetam and the solvent under hypoxic conditions as well as placebo under normoxic conditions. Spectral analysis of the EEG recorded under hypoxia demonstrated neurophysiological alterations indicative of a deterioration in vigilance, which was also reflected by a deterioration in psychomotor activity and mnestic performance in the psychometric tests. Aniracetam i.v. attenuated the hypoxia-induced deterioration of brain function and mental performance, thus exhibiting protective properties against hypoxia in man. The usefulness of the hypoxia model in the screening of antihypoxidotic compounds is discussed.

Adult↗
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

Spontaneous and drug-induced remission of alcoholic organic brain syndrome: clinical, psychometric, and neurophysiological studies.

The spontaneous and drug-induced remission of alcoholic organic brain syndrome was studied in a double-blind, placebo-controlled trial. Forty patients with alcoholic organic brain syndrome (OBS) were randomly assigned to a 6-week treatment with either placebo or piridoxilate, a reciprocal salt between two stereoisomers of the glyoxylic acid-substituted piridoxine. Clinical, psychometric, and computer-assisted spectral analyses of the electroencephalogram (EEG) were carried out in weeks 0, 2, 4, and 6. Piridoxale-5-phosphate (PLP) blood level determination and laboratory investigations were performed before therapy and also in weeks 4 and 6. Both groups of patients demonstrated significant clinical improvement over 6 weeks of treatment, but the improvement in the piridoxilate-treated group was significantly greater than that in the placebo group. This conclusion was also confirmed by psychometric tests demonstrating a greater improvement in attention, concentration, attention variability, tapping, visual and numerical memory, and aftereffect (Archimedean spiral) in the piridoxilate than in the placebo group. Spectral analysis of the EEG showed an increase in alpha and a decrease in fast beta activities in both groups, while delta activity was attenuated only in the piridoxilate-treated group. The latter was found to be significantly correlated with the improvement in psychopathology. The present data confirm previous predictions about the encephalotropic and psychotropic properties of piridoxilate; these predictions were based on pharmaco-EEG trials in the elderly that suggested vigilance-improving qualities of piridoxilate. The reversible alcoholic OBS appears to be a suitable model for the assessment of therapeutic efficacy of nootropic drugs.

Adult↗
PubMed1983

Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine.

1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

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

Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients.

In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed.

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↗
PubMed1982

[Influence of the disco-scene on the psyche and soma of young people: psychometric, computerized-EEG and physiological studies (author's transl)].

Investigating the personality profile of 90 young disco-visitors, it was found that the group on the whole did not differ from the norm. However, a more detailed analysis according to age and sex demonstrated that young female "disco-fans" (under the age of 20 years) exhibited an increased desire for communication and contacts but also a less critical and a more pronounced self-admiring attitude than controls, while this was not observed in males. Subsequently, the effect of a typical disco-night on physiological, neurophysiological and psychometric variables was studied in 13 young disco-visitors. The results suggested an increased activation and arousal as reflected by the increased critical flicker fusion frequency, heart rate and blood pressure. Moreover, psychomotor activity, drive and mood were found to be improved, while attention, concentration, attention variability, reaction time and mnestic function deteriorated as compared with a control night. Digital computer period analysis of the electroencephalogram revealed an increased of theta and beta activity, and a decrease of alpha activity. The profile of the latter CNS changes shows a certain similarity to the pharmaco-EEG profiles of antidepressants. The findings are discussed.

Adult↗
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↗
PubMed1982

Pharmaco-EEG profiles of typical and atypical antidepressants.

Utilizing quantitative analysis of the human electroencephalogram (EEG), the effect of typical and atypical antidepressants on the central nervous systems (CNS) was studied in several double-blind, placebo-controlled trials. At least two types of pharmaco-EEG profiles may be differentiated: 1) a thymeretic, desipramine-like pharmaco-EEG profile suggesting activating properties of the drug (desipramine, tranylcypromine, nomifensine, higher doses of pirlindol and to some extent of fluoxetine); 2) a thymoleptic imipramine- and amitriptyline-like pharmaco-EEG profile showing also sedative qualities (imipramine, amitriptyline, maprotiline, binodaline, danitracene and fluvoxamine). A small number of new compounds exhibit still another pharmaco-EEG profile which may reflect some activating properties different from the above-described ones (clovoxamine, ciclopramine, tandamine). Trazodon on the other hand, produced just opposite changes indicating sedative effects. Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time- and dose-efficacy relations at the target organ--the human brain. The relationships between pharmacodynamics and pharmacokinetics will be discussed.

Adult↗