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Biomedical subjects

A Walser

Publications and source records attributed to A Walser.

At least 37 records · Page 2Linked to original sources
PubMed1983

2-Benzazepines. 4. [1,2,3]Triazolo[4,5-d][2]benzazepines and dibenzo[c,f][1,2,3]triazolo[3,4-a]azepines: synthesis and evaluation as central nervous system agents.

The facile synthesis of [1,2,3]triazolo((4,5-d][2]benzazepines and dibenzo[c,f][1,2,3]triazolo[3,4-a]azepines by the addition of sodium azide to acetylenic benzophenones is described. Examination of the pharmacological data indicates that selected triazolobenzazepines are as potent as diazepam in the anti-pentylenetetrazole test and are weaker in the inclined screen and rotarod tests, suggesting that these compounds have antianxiety properties similar to diazepam with fewer deficits in motor coordination. In addition, a possible diazepam antagonist was found in the triazolo-benzazepine series. The dibenzotriazoloazepines were found to be inactive in four standard CNS screening procedures.

Animals↗
PubMed1983

2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents.

A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less activity in the inclined screen test. A pharmacological data profile is given for 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (7c). The structure-activity relationships of these potential anxiolytic agents are discussed.

Animals↗
PubMed1983

2-benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine.

The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

Animals↗
PubMed1982

Midazolam: radioimmunoassay for pharmacokinetic studies in man.

A specific radioimmunoassay (RIA) for the determination of the new short-acting water soluble imidazo-1,4-benzodiazepine, midazolam, directly in plasma has been developed. Employing 3H-midazolam as the radioligand and a rabbit antiserum to a diazo conjugate of 5'-aminomidazolam and albumin, the method has a limit of sensitivity of 2 ng/ml of midazolam using a 20 microliters sample of plasma. The intra- and inter-assay coefficients of variation ranged from 4 to 7% and 13 to 15%, respectively. The specificity of the RIA was established by demonstrating good agreement with both EC-GC and GC-MS procedures in the analysis of multiple clinical plasma samples. The utility of the RIA for the pharmacokinetic evaluation of midazolam is illustrated with plasma concentration profiles of the drug obtained in subjects who had received midazolam intravenously, intramuscularly and orally.

Animals↗
PubMed1981

Pupil cycle induction test: a way of evaluating the pupillary light reflex.

The Pupil Cycle Induction Test (PCIT) described here is a simple and sensitive clinical method for the evaluation of afferent pupillary defect. It assesses the difficulty in setting up regular and sustained light-induced pupil oscillations, in contrast to methods assessing the light reflex by timing the oscillations. PCIT was applied to 186 presumably normal eyes (with normal visual acuity and normal fundi). In ten eyes, sustained oscillations could not be induced; further investigation showed that four of these eyes had altered visual-evoked response. The test was also carried out in 34 patients suffering from anterior visual pathway disorders. Sustained pupil oscillations could not be set up in 44 out of the 57 affected eyes. In the present series, significant alteration of light-induced pupil oscillations has been observed in several patterns: (1) immediate alteration; (2) delayed interruption of oscillations without spontaneous recovery, and (3) intermittent periods with oscillations of relatively small amplitude lasting more than three pupil cycles. PCIT assesses changes in light threshold for pupil response. It is suggested that delayed and transient alterations of oscillations are related to time-dependent afferent pupil defects similar to intermittent abnormalities of visual function reported in patients with diseases of the optic nerve or the chiasm.

Adolescent↗
PubMed1981

Influence of central depressant drugs on pupil function: an evaluation with the pupil cycle induction test.

Afferent pupillary defect is an early sign of optic nerve or chiasm disease. It can be evaluated by the Pupil Cycle Induction Test (PCIT) which assesses the difficulty in setting up regular and sustained pupil oscillations. PCIT was carried out in 30 subjects with presumably normal visual function (normal visual acuity and normal fundi) and taking benzodiazepines and/or barbiturates. In 42 out of the 60 tested eyes, response to PCIT was altered. This emphasizes the necessity of a detailed drug-taking history when investigating anterior visual pathways by means of pupil function, especially when one considers the extensive use of central nervous system depressant drugs by the general population.

Adolescent↗
PubMed1977

[Effect of combined chemotherapy on the prognosis of Hodgkin's disease: retrospective study of 74 cases from 1959-1973].

In this retrospective study the effect of combined chemotherapy on survival of patients with Hodgkin's disease is investigated. Among 125 cases observed between 1959 and 1973, the survival, response rate and duration of remission of patients treated with single drugs are compared with the same parameters in those treated by polychemotherapy. Further, since the combined treatment schedule was introduced in our group in 1969, survival of patients treated before and after this date is likewise compared. 35% of patients in the single drug group survived for more than 2 years, against 69% in the polychemotherapy group. At 3-year survival, the corresponding values were 12% and 61% respectively. For patients treated before 1969, survival of 2 and 3 years represents 45% and 22%. For patients treated from 1969 to 1973, the corresponding values are 61% and 51%. Rates of complete response are 20% for single drug treatments and 70% for combined treatments. Analysis of the results suggests that these differences correspond to the therapeutic superiority of combined chemotherapy in the treatment of Hodgkin's disease and not to major discrepancies in prognostic factors among the patient groups compared.

Adolescent↗
PubMed1977

Quinazolines and 1,4-benzodiazepines. 81. s-Triazolo[4,3-a][1,4]benzodiazepines by oxidative cyclization of hydrazones.

s-Triazolo[4,3-a][1,4]benzodiazepines bearing various substituents in the 1 position were prepared by oxidative cyclization of the appropriate aldehyde hydrazones of 2-hydrazinobenzodiazepines. Diethyl azodicarboxylate and activated manganese dioxide were used as oxidizing agents. The new triazolo compounds were active in the CNS tests but none of them reached the potency of the known triazolobenzodiazepines.

Animals↗
PubMed1976

Quinazolines and 1,4-benzodiazepines. 75. 7-Hydroxyaminobenzodiazepines and derivatives.

7-Nitro-substituted benzodiazepines were reduced with stannous chloride in a buffered system to the corresponding 7-hydroxyamino derivatives. These compounds were alkylated, acylated, and converted to nitroso and azoxy derivatives. The rearrangement of a hydroxyamine to an aminophenol and its oxidation to an aminoquinone are also exemplified. The results of the pharmacological screening for CNS effects are given.

Animals↗
PubMed1976

Corticotropic action of an intra-nasally applied synthetic ACTH derivative.

The corticotropic action of a synthetic ACTH derivative, D-Ser1 Lys17,18-1-18ACTH, after intranasal insufflation of 1 mg of the peptide was evaluated in 14 normal volunteers. Plasma cortisol and urinary 17-ketogenic steroids and 17-ketosteroids rose significantly over control values in all subjects (P less than 0.001). Plasma cortisol remained above the normal range for comparable clock times for 18 hr, but fell below 15 mug/100 ml after 12 hr. No evidence for suppression of the hypothalamo-pituitary axis was found the day after ACTH administration, as judged by normal plasma and urinary steroid values and normal diurnal variation. Intranasal administration of long-acting ACTH derivatives may provide a simple, painless and effective way to stimulate endogenous corticosteroid secretion.

17-Ketosteroids↗
PubMed1975

Serum thyroxine and thyroxine-binding proteins in chronic renal failure without nephrosis.

Total serum thyroxine (T4), free thyroxine index (FTI), thyroxine binding globulin (TBG) binding capacity, serum albumin, alpha-globulins and urinary protein excretion were measured in 50 patients with chronic renal failure, but without nephrotic syndrome. 25 patients were undergoing chronic hemodialysis. T4 was within the normal range in most patients. There was a tendency to lower T4 values as compared to an age and sex-matched control group, but this did not reach statistical significance. TBG was normal in most patients. 4 patients showed elevated TBG concomitant with elevation of other alpha-globulins. Serum albumin was significantly decreased. No correlation existed between daily protein excretion and TBG or alpha-globulins, but the correlation between serum albumin and proteinuria was highly significant. T4 and proteinuria correlated with borderline significance. A highly significant correlation between T4 and TBG-albumin values was found. No correlation existed between FTI and TBG-albumin levels. The data suggest that T4 and TBG are normal in most patients with renal failure, even in the presence of significant proteinuria. Low T4 values, when found in renal insufficiency, may be secondary to low serum albumin and possibly prealbumin.

Adult↗