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Biomedical subjects

G Wendt

Publications and source records attributed to G Wendt.

At least 55 records · Page 3Linked to original sources

[Brofaromine--a selective, reversible and short-acting MAO-A inhibitor].

During the last years the MAO-inhibitors reached a progressive importance in clinical practice. It was attempted to solve problems of tolerability by a new generation of MAO-inhibitors. Brofaromine is a MAO-inhibitor of the second generation, a selective, reversible and short acting MAO-A-inhibitor, promising that the dangerous "cheese effect" will occur only under extreme conditions. The clinical trials performed hitherto, among other double-blind test versus tranylcypromine and imipramine, demonstrate a good antidepressive efficacy and a good tolerability.

Antidepressive Agents↗

CGP 12.103 A versus clomipramine in the treatment of depressed inpatients--results of a double-blind study.

In a double-blind study, which was conducted as an interindividual comparison, 41 depressed inpatients were divided into two test groups according to a randomized list and received either the test substance CGP 12.103 A (19 patients) or the comparative substance clomipramine (22 patients). The study was conducted over a period of 28 days and the dosage of each substance, after being gradually increased, was stabilized at 150 mg. Except for a significantly varied distribution of syndrome patterns, the two treatment groups were comparable with regard to relevant criteria. Both treatment groups showed a significant improvement as assessed by both the degree of severity of depression and the Hamilton Depression Rating Scale; on each scale, however, the clomipramine treatment group exhibited a tendency toward better antidepressive efficacy. According to the self-evaluations of the patients, which were conducted with the help of v. Zerssen's Self-Rating Scale, this tendency was not significant. The Kusta activation parameter indicated a tendentially stronger manifestation in the case of clomipramine. In the final evaluation the onset of efficacy for the CGP 12.103 A group lay in the mean on treatment day 6, for the clomipramine group on treatment day 10. The physician's overall assessment of therapeutic effect found no differences between the two treatment groups on day 14 and on day 28. Expected side effects were observed in the CGP 12.103 A group in nine patients, in the clomipramine group in 14. All in all, the test substance CGP 12.103 A, the (-) or R-enantiomer of the antidepressant oxaprotiline, which itself is derived from maprotiline, showed no essential differences in its antidepressive efficacy compared with clomipramine.

Anthracenes↗

First clinical experience with ifoxetine, a new 5-HT reuptake blocker with particular emphasis on the side-effect profile of the 5-HT-uptake inhibiting drugs.

Ifoxetine (CGP 15 210 G) is a novel and unusual drug. It specifically and selectively blocks the 5-HT reuptake in the brain without affecting the 5-HT uptake processes in the periphery (blood platelets). In the first, open and explorative trials its tolerability and effectiveness were studied in 33 patients suffering from endogenous (n = 25) or other types of depressive disorders. In daily doses of 50 to maximally 300 mg mental condition considerably improved in 17 patients. As assessed by HAMD 7 patients out of 17 became asymptomatic (HAMD Score less than 10) whereas 10 other patients markedly improved (decrease in HAMD by greater than or equal to 50%) in the course of 3 to 4 weeks of treatment. Eleven patients improved only slightly, in 3 patients no particular change in condition could be observed and 2 patients deteriorated. This deterioration was due to psychotic decompensation after the second week of the treatment (75-100 mg/d). Apart from this, ifoxetine was well tolerated particularly at doses of 50-150 mg/day, which also appeared to be the optimal therapeutic range of doses. There were no changes in cardiovascular function or laboratory values and almost no somatic or other complaints of major concern. These preliminary results indicate that ifoxetine has antidepressant properties with possibly an advantageous side-effect profile, in comparison to other 5-HT uptake inhibitors.

Adult↗

Double-blind study of oxaprotiline versus clomipramine in the treatment of depressive inpatients.

In a double-blind study on 38 unselected depressive inpatients (19 per group) suffering from endogenous and psychogenic depression, oxaprotiline, a new tetracyclic compound, a hydroxylized maprotiline with a highly selective norepinephrine reuptake inhibition, was compared with clomipramine over a period of 28 days in a daily dosage of 150 mg. Both drugs were found to be approximately equivalent and with no significant differences due to the overall assessment of the reduction of depression severity and amelioration of goal symptoms. This was also reflected in the results of the Hamilton Depression Scale and the self-rating scales for depression (SDS, Bf-S, ESTA).

Adult↗

Controlled trial on the possible advantages of a combined therapy with maprotiline and haloperidol in endogenous depression.

There is some clinical evidence that neuroleptics are able to increase the therapeutic effect of antidepressant drugs. From a theoretical viewpoint this could be due to influences on pharmacokinetics or receptor sensitivity. In a controlled three-week trial in 28 patients with endogenous depression the potential advantages of a combined medication of 150 mg maprotiline and 9 mg haloperidol per day (given for the first six days) in comparison with monotherapy with maprotiline were tested. Neither during the time of combined medication nor following withdrawal of haloperidol did this treatment regimen show better clinical results in comparison with controls. In keeping with results described elsewhere, the serum levels of the antidepressant, but not of its desmethyl metabolite, were higher in the experimental group.

Adult↗

The Community Study Stuttgart.

A basic objective of the "Community Study Stuttgart", a part of the German Cardiovascular Prevention Study (GCP), which began in April 1984 and will end in December 1991, is to develop and utilize globally applicable intervention measures through which cardiovascular risk factors can be reduced effectively under the population's living conditions in the Federal Republic of Germany. Vital elements of intervention include exerting influence on individual health behaviour as well as creating and developing community structures and provisions to foster health. The intervention is directed towards behaviour in the sectors of nutrition, physical activity and (non-)smoking, but psychosocial constellations will also be taken into consideration. The long-range goal of the study is a reduction in the incidence of ischaemic heart diseases and cerebrovascular diseases (as well as the ensuring reduction in total mortality) among the community populations as compared to the average population of the same age in the Federal Republic of Germany. The intervention concept is based on a broadened pathogenetic chain in which the so-called classic somatic risk factors for cardiovascular diseases have been supplemented by behaviour-related psychosocial factors and living conditions which influence health behaviour. Each of the target variables is significant in itself within the intervention concept. In the study, it is assumed that the community framework is of essential relevance to daily life and affects community members' knowledge, attitudes and opportunities for realization. On the basis of scientific studies on the lifestyle concept, an intervention concept was developed which centres on the population of defined communities.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗

Determination of pyrrolidinone in plasma by high-performance liquid chromatography.

A sensitive and selective high-performance liquid chromatographic method for the determination of pyrrolidinone (I) in plasma is described. Compound I was extracted from plasma with methylene chloride using kieselguhr as aqueous phase support. The gamma-aminobutyric acid (II) formed after alkaline hydrolysis of I was derivatised with o-phthalaldehyde, chromatographed on a reversed-phase column, and quantified by fluorescence detection. The limit of quantification was 2.5 ng/ml (intra-assay R.S.D. 5%) using a 1-ml plasma sample. The inter-assay precision was 3-14% (R.S.D.) over the concentration range 2000-5 ng/ml, and the recovery from plasma was quantitative (99.3 +/- 2.9%). The accuracy of this method was established from the good agreement between the values obtained after the analysis of plasma samples by both this method and a gas chromatography--mass spectrometry method. The high-performance liquid chromatographic procedure was applied to the determination of (a) endogenous I in human plasma samples and (b) I in plasma following intravenous administration of this substance to a dog. In twelve human subjects, endogenous concentrations of I of 8.3 +/- 2.3 ng/ml (gas chromatography--mass spectrometry method: 6.1 +/- 2.6 ng/ml) were found.

Animals↗

2-Pyrrolidinone and succinimide endogenously present in several mammalian species.

2-Pyrrolidinone and succinimide were identified in blood plasma of man, rat, and mouse. Dog plasma contained only traces of 2-pyrrolidinone not exceeding significantly the detection limit of our GCMS-method. Succinimide but not 2-pyrrolidinone could also be found in the brains of rat and mouse. Evidence is presented for a metabolic pathway leading from 2-pyrrolidinone to succinimide, with 5-hydroxy-2-pyrrolidinone as an intermediate.

Adult↗

Determination of tiapamil and of its two main metabolites in plasma and in urine by high-performance liquid chromatography.

Selective high-performance liquid chromatographic methods for the determination of tiapamil and its two main metabolites in plasma and urine are described. Tiapamil together with its metabolites is extracted at alkaline pH into dichloromethane. Separation is carried out using normal-phase high-performance liquid chromatography with ultraviolet detection (278 nm). The unchanged drug and the desmethyl metabolite are analysed simultaneously. The second metabolite is analysed separately under more polar conditions. The sensitivity limits are 50 ng/ml for tiapamil, 100 ng/ml for the desmethyl metabolite and 75 ng/ml for the second metabolite, using 0.5 ml of plasma. The sensitivity limits in urine are 100 ng/ml for all three compounds using a 0.5 ml specimen. The method has been applied to the analysis of human plasma and urine after intravenous (70 mg) and oral (400 mg) administration of tiapamil.

Biotransformation↗

Serial M-mode echocardiography in evaluation of the cardiovascular effects of tiapamil and their relationship to plasma levels in patients with coronary heart disease.

Tiapamil (Ro 11-1781) is a new calcium antagonist. Several investigators have reported about its efficacy against cardiac arrhythmias and angina pectoris. However, there was no study that assessed a possible relationship between hemodynamic effects and plasma concentration. Our study was aimed to investigate any possible relationship between cardiovascular effects of tiapamil and its plasma concentration. We selected 8 coronary; patients (6 males and 2 females) with a mean age of 61.9 yr and a mean weight of 70.9 kg. Tiapamil was administered per os at the dose of 250 mg t.i.d. for 4 consecutive days. Hemodynamic data were obtained by means of echocardiography, ECG and sphygmomanometry. Plasma concentrations of Ro 11-1781 and its major metabolites were measured by means of high pressure liquid chromatography. With tiapamil, the morning systolic BP fell from 130.6 +/- 19.5 (mean +/- SD, pretreatment) to 114.4 +/- 18.2 mm Hg on day 4, the change being clinically and statistically significant (P less than 0.02 by paired t-tests). Diastolic BP and HR remained unchanged. LVEDD and LVESD were not affected to any relevant extent, but VCF was significantly (P less than 0.05) and persistently increased. Tiapamil was well absorbed, but large interindividual variations were observed. As a general rule, no direct relationship between plasma concentrations and hemodynamic effects could be demonstrated. However, the number of patients is too small to allow general conclusions. At the above dose, tiapamil did not elicit any clinically detectable negative inotropic or negative chronotropic effect, probably because of its lowering effect on systolic BP.

Aged↗