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Biomedical subjects

C Stumpf

Publications and source records attributed to C Stumpf.

At least 37 records · Page 2Linked to original sources

Pharmacological actions of central nervous system depressants given intravenously as suspensions.

Three central nervous system (CNS) depressants, methohexital (sodium), midazolam (maleate), and flunitrazepam, were given intravenously to rabbits in equimolar doses as suspensions and solutions. The mean diameters of the particles in the suspensions were 770, 840, and 460 nm, respectively. The CNS actions were verified by recording the bioelectrical activity of the precentral cortex. The suspensions were tolerated well. There were no differences in onset, duration, and maximal intensity of action between suspension and solution of each drug. The results of this study should facilitate pharmacological studies of drugs acting on the CNS that are insoluble in water.

Animals↗

Synchronizing effect of the alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine on rabbit electroencephalogram.

The selective alpha 1-adrenoceptor agonist St 587 (2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine) was tested in conscious rabbits in the dose range of 0.125 to 8 mg/kg cumulatively i.v. In cardiovascular experiments St 587 increased mean arterial blood pressure and decreased heart rate in a dose dependent manner. In neuropharmacological experiments St 587 induced a biphasic EEG effect, an EEG synchronization preceded by a short period of cortical arousal. The duration of both EEG phenomena increased with increasing doses. There was no correlation between rise in blood pressure and EEG arousal reaction as periods of precentral spindling appeared also during maximal increase in blood pressure. Both, EEG synchronization and arousal reaction could be antagonized by the alpha 1-adrenoceptor antagonist prazosin, 1-2 mg/kg i.v. From these experiments it is concluded that the main effect of the alpha 1-adrenoceptor agonist St 587 in rabbits is EEG synchronization, i.e. sedation. Furthermore a barbiturate antagonism by high doses of St 587 was shown and this is explained by the initial arousal reaction as observed after injection of St 587.

Animals↗

Differentiation of drug-induced rhythmical activities in the rabbit's brain by a benzodiazepine antagonist.

The effect of a benzodiazepine antagonist, ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788), on the cerebello-rubral rhythm induced by a water soluble benzodiazepine derivative (medazepam hydrochloride) or by a barbiturate (pentobarbital sodium) was investigated in the rabbit. The frequency of this rhythm which depends on the depth of the central depression caused by either of these agents was used for the drug interaction study. Ro 15-1788 when given alone up to 10 mg/kg did not cause any changes in the cerebello-rubral and the neocortical electrical activities. Ro 15-1788 (0.5 and 2.0 mg/kg) was effective in antagonizing the medazepam-induced cerebello-rubral rhythm and the rhythmic discharges of Purkinje cells in a dose-dependent manner. The antagonistic effect was also observed in the electrocorticogram. The pentobarbital-induced cerebello-rubral rhythm and the neocortical activity were not influenced by Ro 15-1788 up to 5 mg/kg. Thus, the similar effect of barbiturates and benzodiazepine derivatives on the cerebello-rubral system seems to be mediated by different pharmacodynamic actions. The findings are in line with previous studies indicating a selective antagonism of Ro 15-1788 and benzodiazepine derivatives.

Animals↗

Failure of 6-aminonicotinamide in selectively damaging astrocytes in vitro.

The present study investigates cytotoxic effects of 6-amino-nicotinamide (6-AN), a nicotinamide antagonist, in primary cultures of the dissociated postnatal mouse cerebellum. Initial effects were seen with 1.5 microM 6-AN of this substance included in the culture medium at plating. Established cultures responded to concentrations higher than 3.1 microM. The relative number of astrocytes (identified immunohistochemically) was not reduced in cultures exposed to low, but effective concentrations of 6-AN. We therefore conclude that 6-AN is no suitable agent to regulate the number of astrocytes in cell cultures. Thus, at the present alpha-aminoadipic acid remains the only substance which can be considered a selective gliotoxin in vivo and in vitro.

6-Aminonicotinamide↗

[Thrombocytopenia in pregnancy].

The rare occurrence of thrombocytopenia in pregnancy is reported. Our own procedure in pregnancy and delivery is described in detail. The differential diagnostic considerations are emphasized. The present situation with regard to therapy is discussed with reference to the available literature.

Adult↗

Drug-induced rhythmic burst activity of cerebellar neurons.

The discharge of cerebellar neurons was investigated in the rabbit and the rat under the influence of pentobarbital, diazepam or medazepam. In the rabbit, these drugs are known to induce a rhythm ranging between 4 and 25 Hz in the red nucleus (RN) and the cerebellum (Cb). Purkinje cells (P cells) in the intermediate zone of the cerebellar cortex as well as neurons of the interposed nucleus (IPN) were found to discharge with burst patterns fully synchronized with the drug-induced RN rhythm. In contrast, P cells in the medial cerebellar zone responded to these drugs only with changes in their discharge rate. Since P cells of the intermediate longitudinal zone project to the RN mainly via the IPN, the present findings complement our previous results, indicating that the rhythmic electrical activity in the RN is initiated by the cerebellum. The three drugs had similar effects on the activity of cerebellar units in the rabbit and the rat. The investigation also shows that, in spite of the uniform morphological structure of the cerebellar cortex, P cells do not respond uniformly to a given drug: the diversity of findings published on the P cell response to barbiturates or benzodiazepine derivatives may be explained by differences in the recording sites.

Animals↗

Pharmaco-EEG experiments in animals.

The principles of pharmaco-EEG experiments are reviewed from the standpoint of a pharmacologist. Pharmaco-EEG experiments may serve one of three purposes: they may be used as a model, as an index or as a tool in a pharmacological study. Several examples are given for each of these three different lines of research.

Animals↗

[Electroencephalographic Investigations of 4-Aminopyridine (author's transl)].

Electroencephalographic investigations of 4-aminopyridine were carried out in the non-anesthetized, immobilized rat. Under the influence of this agent seizure-like activity appeared in the hippocampal and subsequently in the neocortical recordings. This effect was antagonized by pretreatment with diazepam. The discussion deals with the central cholinergic action of 4-aminopyridine.

4-Aminopyridine↗

Isolation of replication forks from growing Ehrlich ascites cells.

A procedure is described which permits the large-scale isolation of essentially complete replications forks from the DNA of Ehrlich ascites cells. The whole nuclear DNA is first isolated by a method which involves minimal hydrodynamic shear. The DNA is then degraded by cryolysis, a freeze-thawing procedure, to a size providing the otherwise very labile forked structures with a sufficient resistance against shear forces. Finally, the Y-shaped structures of replicating DNA are separated by nitrocellulose column chromatography. When the newly formed strands of replicating DNA were density-labeled with 5-bromodeoxyuridine the DNA fraction isolated by this procedure banded in isopycnic CsCl gradients at a density expected for Y-shaped molecules with two light-heavy branches and one light-light branch and sedimented significantly faster than the corresponding bulk DNA fraction through neutral sucrose gradients. The forked molecules could be visualized by electron microscopy. The essential step of the procedure is the cryolysis which produces fragments from larger DNA structure essentially at random. When the cryolysis is omitted the forked structures are disrupted within the highly susceptible regions around the branching point.

Animals↗

[Interactions between nitrous oxide and central depressants].

The combined effects on mice of N2O and various central depressants were investigated. A loss of the righting reflex was taken as the criterion for the drug effects. Essential differences could be demonstrated in the type of interaction: diazepam, flunitrazepam, and medazepam have a supra-additive effect in combination with N2O; the solvent of diazepam and an experimental product, Ro 21-3981 (8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo [1,5-a] [1,4]-benzodiazepine maleate) a simply additive one. However, the interactions between N2O and barbiturates (pentobarbitone and phenobarbitone), and N2O and ethanol were found to be infra-additive. The results of this and previous investigations indicate that additive or supra-additive interactions can only be expected in those cases in which at most one of the two active ingredients in addition to its depressive effect also exhibits an excitatory component.

Animals↗

Effect of harmaline on the cerebello-rubral system.

Harmaline induces synchronous rhythms in both the cerebellum and the red nucleus of the rabbit. The level of synchronization is lower in the red nucleus than in the cerebellar cortex, probably because the cerebello-rubral pathway and the red nucleus neurons only participate poorly in the harmaline-induced olivo-cerebellar rhythm.

Alkaloids↗

[Effect of combined application of halothane and some central depressants (author's transl)].

The combined effects of halothane and various central depressants were studied in mice by means of an isobolographic method which allows the statistical evaluation of interactions. A loss of the righting reflex for at least 2 min was taken as the criterion for the synchronisation of the peak time of drug effects. All interactions turned out to be supra-additive, more pronounced in the case of diazepam and flunitrazepam than in the case of medazepam, pentobarbitone or ethanol. The organic solvent used for the solution of diazepam and flunitrazepam was found to contribute to the observed interactions. The difficulties of estimating and classifying combined drug effects as well as their clinical relevance are discussed.

Anesthesia, Inhalation↗

Neurotoxicity and CSF level of three penicillins.

The electrocortical activity and the antibiotic concentration in serum and CSF were investigated in rabbits after i.v. administration of benzylpenicillin, ampicillin and oxacillin. In contrast to ampicillin and oxacillin, benzylpenicillin induced a pronounced epileptogenic activity. The different epileptogenic activity of the three penicillins cannot be explained by the difference in the CSF level of these agents only. The intensity of the epileptogenic activity and the CSF level after benzylpenicillin administration were markedly influenced by the experimental procedure in that curarized animals exhibited both higher CSF levels and more intense seizure activities than non-curarized animals. Factors are discussed which may be responsible for the different neurotoxic potency of the three penicillins and for the dependence of the benzylpenicillin-induced seizure intensity on the experimental procedure.

Ampicillin↗

[Action of central depressants on the nitrous oxide anesthesia (author's transl)].

The synergistic action of seven central depressants three benzodiazepines, two neuroleptics on barbiturate and morphine on the anesthetic activity of nitrous oxide was studied in mice. The benzodiazipines and among them nitrazepam and flunitrazepam were found to be the most potent drugs in this respect; morphine on the other hand was innefective even in toxic doses. There was a significant difference in the slope of log dose-response curves; these curves were much steeper for pentobarbitone, droperidol and chlorpromazine than for nitrazepam, flunitrazepam, and diazepam. The theoretical and practical implications of this difference are discussed.

Anesthesia, Inhalation↗

Action of six commonly used benzodiazepines on isolated guinea-pig ileum preparation.

The spasmolytic activity of six commonly used benzodiazepines was investigated on isolated guinea-pig ileum preparation. All six substances proved to be non-competitive antagonists of carbachol and barium chloride, the pD'2 values ranging between 3.23 and 4.37 in the presence of either agonist. The significance of these findings is discussed.

Animals↗