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Biomedical subjects

B Saletu

Publications and source records attributed to B Saletu.

At least 199 records · Page 11Linked to original sources
PubMed1981

Traffic noise-induced sleep disturbances and their correction by an anxiolytic sedative, OX-373.

In a double-blind, placebo-controlled study the effect of nocturnal traffic noise and bedtime medication of a new benzodiazepine, OX-373, on objective and subjective sleep variables as well as on the quality of morning awakenings was investigated. 10 healthy subjects spent 17 nights in the sleep laboratory: 2 adaptation nights, 1 baseline night, 4 drug nights (20, 30, and 40 mg OX-373 and placebo) and 4 subsequent wash-out nights as well as 3 nights under traffic noise with placebo, 30 and 40 mg OX-373 and 3 subsequent wash-out nights. Nocturnal traffic noise with an intensity of 45-65 dB(A) induced sleep disturbances characterized by an increase in intermittent wakefulness and stage 1 and the number of nocturnal awakenings as well as by a decrease of spindle and REM sleep stages. Subjectively, a decrease of deep sleep and increase of light sleep and middle insomnia was reported. Upon awakening in the morning, mood was significantly deteriorated. The new benzodiazepine OX-373 attenuated the above-described traffic noise-induced changes and produced even oppositional alterations, such as a decrease in stage 1, number of awakenings and stage shifts while increasing stage 2. The drug alone decreased the number of awakenings and stage 1 and augmented stage 4 as compared with placebo, which was subjectively felt as an increase in deep sleep and as a decrease of light sleep, early and middle insomnia. In the morning, there were no signs of 'hangover', which was confirmed also by psychometry. Nor were there any clinically relevant alterations in blood pressure and pulse. Thus, our studies confirmed earlier pharmaco-EEG and psychometric investigations predicting OX-373 as well-tolerated anxiolytic sedative, and suggested further that traffic noise could eventually be utilized as an experimental provocative technique in order to induce a standardized sleep disturbance for early clinical drug evaluation of potentially hypnotic substances.

Adult↗
PubMed1980

Clovoxamine and fluvoxamine-2 biogenic amine re-uptake inhibiting antidepressants: quantitative EEG, psychometric and pharmacokinetic studies in man.

In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxamine and in 8 out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Adult↗
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↗
PubMed1979

Evaluation of pharmacodynamic properties of psychotropic drugs: quanitative EEG, psychometric and blood level investigations in normals and patients.

Quantitative EEG analyses in combination with certain statistical procedures may be utilized in order to classify psychotropic drugs and to determine their cerebral bioavailability. Psychometric tests including evaluation of attention, concentration, psychomotor activity, critical flicker frequency, reaction time, Archimedean spiral, mood and affectivity, may add valuable information about a drug's psychotropic and pharmacodynamic properties. As was seen in studies involving a new pyridodiazepine, short-term drug effects in the EEG of normals are predictive of EEG and clinical effects in patients. Pharmaco-EEG profiles of lopirazepam were found similar in normals and alcoholic patients with an anxiety syndrom as far as the type of changes was concerned, although some quantitative differences were observed. As previously described, quantitative EEG changes during treatment were correlated with clinical improvement or deterioration. Moreover, there is some evidence that single dose effects in the EEG of patients may eventually be utilized to predict therapeutic outcome with a certain drug. Finally, relationships between blood level, quantitative EEG and psychometric changes after administration of phentermine and oxazepam are described and discussed.

Arousal↗
PubMed1979

[Repolarisation disturbances in the ECG under antidepressant drugs. A comparison of two drugs, differing in chemical structure and pharmacological profile (author's transl)].

In connection with clinical drug trials we compared the ECG-recordings during application of two different antidepressants. Tandamine (AY 23946) is a tricyclic drug with main effects on the norepinephrine reuptake, Fluvoxamine (DU 23 000) a nontricyclic antidepressant with a selective effect on the serotonin reuptake. No differences were observed regarding both frequency and patterns of the repolarisation disturbances. Thus, it appears that the chemical structure of the drug is not responsible for the "typical" form of the repolarisation disturbances. We further hypothesize that toxic effects and regulatory mechanisms of the cardiovascular system, caused by changes in norepinephrine and 5-hydroxytryptamine levels may be responsible for the areforementioned ECG aberrations.

Adult↗
PubMed1979

Classification and bioavailability studies with WE 941 by quantitative pharmaco-EEG and clinical analyses.

Psychoactivity, pharmacodynamic properties and drug tolerance of 2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]1,2-(4-triazolo)[4,3-a][1,4]diazepine (WE 941), a new triazolodiazepine, were studied in 10 normal subjects utilizing quantitative pharmaco-EEG and clinical evaluation methods. In the double-blind, placebo-controlled trial, the subjects received randomized at weekly intervals oral single doses of 0.1 mg, 0.3 mg and 0.5 mg WE 941, placebo, and 30 mg flurazepam as reference substance. Measurements were obtained before and at the 2nd, 4th, 6th h post drug. EEG power spectral density analysis demonstrated no changes after placebo, while WE 941 and flurazepam induced statistically significant alterations characterized by an increase in beta-activity, a decrease in alpha-activity and increase in average frequency ("anxiolytic pharmaco-EEG profile"). In addition, 0.3 mg and 0.5 mg WE 941 and 30 mg flurazepam produced a significant augmentation of delta-activity indicating hypnotic qualities. Considering spontaneous and placebo-induced alterations, evaluation of the time- and dose-effect relationship indicated that all active substances exerted a tranquilizing effect throughout 8 h, while the hypnotic properties of 0.1 mg WE 941 were minimal (up to the 4th h), those of 0.3 mg WE 941 were moderate (up to 6 h) and those of 0.5 mg WE 941 were marked (up to 8 h). The dosage equipotent to 30 mg flurazepam is 0.3 mg WE 941. Heart rate and blood pressure exhibited no relevant changes, while side effects including fatigue, drowsiness and dizziness were mostly observed after the highest dosage of WE 941.

Adult↗
PubMed1978

Treatment of the alcoholic organic brain syndrome with EMD 21657. A derivative of a pyritinolmetabolite: double-blind clinical, quantitative EEG and psychometric studies.

The efficacy of EMD 21657--a derivative of a pyritinolmetabolite--with regard to the improvement of the organic brain syndrome (OBS) of chronic alcoholics was investigated in a double-blind study utilizing clinical, psychometric and quantitative EEG evaluation. Nineteen patients received 3 x 300 mg EMD and 21 patients 3 x 1 dragee placebo for 6 weeks. The groups did not differ in regard to age, sex, weight, height, alcohol anamnesis or IQ. The hospitalized patients were examined before as well as at the end of the second, fourth and sixth week of drug treatment. While the overall evaluation by the psychiatrist and patients at the end of the period of treatment did not show marked intergroup differences, the clinical global impression scale and the OBS rating scale demonstrated that both groups showed a significant reduction in their OBS and that improvement with EMD 21657 therapy was significantly superior to the one with placebo. Psychometric analysis also exhibited a significant superiority of EMD in regard to the general, associative, numeric and total verbal memory, concentration and attention variability. Psychovisual memory and the quantative aspects of attention showed opposite findings. Flickerlight fusion frequency, reaction time and after-image did not change significantly. The psychomotor activity improved significantly more with EMD than placebo; this was especially pronounced in the left hand. Affect and mood improved also more with EMD than placebo. Side effects were observed more frequently under active treatment and were characterized by temporary headaches. Power spectral density analysis of the EEG revealed in both groups a decrease of delta, fast alpha and beta activities and an increase in theta and slow alpha activity, but changes during EMD treatment more frequently reached the level of statistical significance than with placebo. The most consistant finding was the theta augmentation under EMD treatment. It was concluded that EMD 21657 is a CNS-effective drug with pronounced nootropic and slight thymotropic properties.

Adult↗
PubMed1978

Accelerated remission of the alcoholic organic brain syndrome with EMD 21657. Double-blind clinical and psychometric trials.

The efficacy of EMD 21657--a derivative of a pyritinol metabolite--on the alcoholic orangic brain syndrome (OBS)) was investigated in a double-blind placebo-controlled study. 19 patients received 3X300 mg EMD, 21 patients 3X1 dragée placebo throughout 6 weeks. The two groups did not differ as to age, sex, weight, height, alcohol anamnesis and IQ. Investigations were carried out before and at the end of the 2nd, 4th and 6th weeks of drug treatment. While an overall evaluation by doctor and patient at the end of the therapy did not reveal any signficant differences, it was found by means of the global score and OBS score that the OBS improved under both substances, but significantly more so with EMD. Psychometric analysis demonstrated that EMD was superior to placebo in regard to general, associative and numeric memory, concentration and attention variability, psychomotor activity, affect and mood, while the Benton test and attention showed opposite findings. Side effects were observed more under EMD than placebo therapy and consisted of temporary headaches and dizziness. Our findings demonstrated that EMD 21657 has pronounced nootropic and some thymotropic effects.

Adult↗
PubMed1977

Fluvoxamine-a new serotonin re-uptake inhibitor: first clinical and psychometric experiences in depressed patients.

The clinical efficacy of fluvoxamine (DU 23000)--the first selective serotonin re-uptake inhibitor of the new class of 2-aminoethyloximethers of aralkylketones was investigated in endormorphous depressed patients during 5 weeks treatment with mean daily dosages of approximately 150 mg DU 23000. A marked and statistically significant improvement of the overall and detailed psychopathology was noted by means of the Global Clinical Impression and Hamilton Rating Scale as early as in the first week of drug administration. Bipolar patients tended to improve more than unipolar ones, retarded depressions more than agitated ones. An additional anxiolytic medication was occasionally required. The drug was well tolerated. Psychometric and laboratory findings did not show any significant changes. The findings are discussed in the light of the indolamine hypothesis of depression.

Adult↗