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Biomedical subjects

H Fink

Publications and source records attributed to H Fink.

At least 19 recordsLinked to original sources
PubMed1991

2-Bromolisuride, an ergot derivative, with dopamine antagonistic and serotonin agonistic properties.

The open-field test was used to study the involvement of dopaminergic and serotonergic mechanisms in the effects of 2-bromolisuride on locomotor activity in the rat. 2-Bromolisuride produced a dose-dependent inhibition of spontaneous locomotor activity. This is most likely due to an antagonistic action at postsynaptic dopamine receptors. Low doses of 2-bromolisuride potentiated apomorphine-induced hypermotility. This potentiating effect was not mediated by a blockade of presynaptic dopamine receptors, because it was not prevented by 6-OHDA lesion of the nucleus accumbens. The potentiating effect of 2-bromolisuride was completely blocked by the serotonin antagonists cyproheptadine and ritanserin. It is suggested that 2-bromolisuride possesses dopamine antagonistic and serotonin agonistic properties.

Animals↗
PubMed1991

CCK-8 modulates D2 receptor agonist-induced hypermotility in the nucleus accumbens.

The influence of CCK-8 on locomotor effects associated with independent D2 receptor stimulation was studied. To selectively stimulate mesolimbic D2 receptors LY 171555 was injected into the nucleus accumbens of awake rats. Locomotor activity was measured in the open-field test. LY 171555 induced a biphasic effect: low doses stimulated, whereas higher doses inhibited locomotor activity. CCK-8 injected into the posteromedial part of the nucleus accumbens suppressed hyperlocomotion induced by LY 171555. The CCK-8 effect was prevented by the CCK-antagonist L 364,718. Our results indicate that CCK-8 modulates D2 receptor-mediated effects in the mesolimbic system.

Animals↗
PubMed1990

Atypical neuroleptics suppress dopaminergic behavioral supersensitivity.

Seven days after bilateral 6-OHDA denervation of the nucleus accumbens locomotor activity was recorded in rats. 6-OHDA lesion strongly enhanced hypermotility induced by apomorphine (1.0 mg/kg IP) as a sign of behavioral dopaminergic supersensitivity. The potency of the classical neuroleptic haloperidol (0.03-0.25 mg/kg IP) to antagonize apomorphine-induced hypermotility was reduced in 6-OHDA-pretreated rats. The atypical neuroleptics sulpiride (5.0-20.0 mg/kg IP), thioridazine (1.0-5.25 mg/kg IP) and clozapine (0.5-2.0 mg/kg IP) and the 5-HT antagonists cyproheptadine (0.2 mg/kg IP) and ritanserin (0.01 mg/kg IP) suppressed the augmented apomorphine response in 6-OHDA-lesioned animals to the level of the apomorphine effect in controls. It is concluded that the model of denervation supersensitivity is capable of differentiating typical and atypical neuroleptics. The abolition of the 6-OHDA-induced increase of the apomorphine hypermotility by the atypical neuroleptics cannot be explained solely by postsynaptic dopamine receptor antagonism. Serotonergic mechanism may be involved in this action.

Animals↗
PubMed1990

[Biochemical aspects of the evaluation of fixed drug combinations].

Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The quantification of eight enzymes from the ageing rat lens, with respect to sex differences and special reference to aldolase.

Eight enzymes, e.g. lactate dehydrogenase, malate dehydrogenase, fructose-diphosphate aldolase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase, hexokinase, phosphofructokinase and pyruvate kinase were estimated quantitatively in the rat lens from 37 to 1,211 days of age, by spectrophotometric methods. The activity was expressed as mU/g LWW. All enzymes measured showed declining activities, but LDH, ALD, SDH, G-6-PDH, HK and PFK gave a significant decrease during ageing when plotted semi-logarithmically from 37 to 1,211 days. SDH and G-6-PDH showed a statistically significant difference between the enzymes from the male and the female lenses. The female lens always had a lower activity than the male lens. Of all enzymes the specific activity, expressed as mU/l mg protein, was calculated. This specific activity appeared to be rather constant during ageing, except for ALD. In the female lenses, the specific activity of 7 enzymes was lower than in the male lenses. For ALD the specific activity decreased significantly in the male lens from 5.32 at 37 days to 0.88 at 1,211 days. In the female lens this significant decrease was from 4.97 to 0.81.

Aging↗
PubMed1986

Behavioral function of GABA in the median raphe nucleus.

Locomotor hyperactivity of rats was induced by injection of muscimol into the median raphe nucleus. Intra-raphe injection of picrotoxin or bicuculline failed to influence locomotor activity, however, muscimol-induced hyperactivity was inhibited by simultaneous intra-raphe injection of picrotoxin and muscimol. These data indicate an involvement of the GABAergic system in the median raphe nucleus in induction of locomotor effects. Systemic and intra-raphe injection of cyproheptadine depressed muscimol-induced hypermotility, whereas lesion of serotonergic raphe neurons by 5,7-DHT or intra-raphe injected LSD did not influence the muscimol effect, suggesting that GABAergically induced locomotor effects are not entirely mediated by serotonergic mechanisms.

Animals↗
PubMed1985

Locomotor effects of lisuride: a consequence of dopaminergic and serotonergic actions.

The open-field test was used to study the involvement of serotonergic and dopaminergic mechanisms in the action of lisuride on locomotor activity in the rat. Lisuride produced a biphasic locomotor effect. The maximum locomotor stimulatory response of lisuride was stronger than that of apomorphine and comparable with that of apomorphine and LSD combined. Hypermotility induced by high doses of lisuride was partially suppressed by the serotonin antagonist cyproheptadine and not further enhanced by LSD. A moderate dose of lisuride potentiated apomorphine-induced hypermotility in the same manner as has been shown for LSD. Lesion of dopaminergic structures within the median raphe nucleus by 6-OHDA produced a potentiation of lisuride-induced hypermotility. This effect was suppressed by cyproheptadine. The locomotor inhibitory effect of low doses of lisuride may be related to a stimulation of presynaptic mesolimbic dopamine receptors. It is concluded that the locomotor stimulant effect of higher doses of lisuride may depend on stimulation of postsynaptic dopamine receptors and a serotonergic action and that the locomotor effects of lisuride reflect a complex interaction at dopaminergic and serotonergic transmission systems.

Animals↗
PubMed1985

Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens.

Intra-accumbens injection of sulpiride, tiapride, and metoclopramide antagonized locomotor hyperactivity induced by intraperitoneal administration of apomorphine in rats and measured over the first five minutes after introducing the animal to an open-field cage. Sulpiride was slightly more potent than tiapride which was more than 10 times more potent than metoclopramide and haloperidol. The threshold dose of sulpiride was as low as 0.001 microgram, bilaterally. Intra-accumbens injection of sulpiride also blocked exploratory hypermotility induced by bilateral intra-accumbens injections of apomorphine and picrotoxin. The threshold dose of sulpiride for blocking these two effects was about 0.01 microgram, bilaterally. Sulpiride was more than 10 times more potent than haloperidol in blocking this apomorphine-induced hypermotility. Haloperidol did not influence the picrotoxin hypermotility. The results obtained indicate strong postsynaptic dopamine antagonist properties of sulpiride, tiapride and metoclopramide.

Animals↗
PubMed1985

Effect of a novel environment on locomotor hyperactivity of rats induced by apomorphine in the nucleus accumbens.

Bilateral local injections into the nucleus accumbens of apomorphine in doses between 0.125 and 20 micrograms produced a dose-dependent increase of locomotor activity in rats recorded over the first 5-min period after placing the animals in a novel environment 7 min after the injection. Continuous records over consecutive 5-min periods revealed that the locomotor effect of apomorphine (1 microgram, bilaterally) declines rapidly within less than 30 min. Progressively weaker locomotor hyperactivity in the first 5-min periods was observed after prolongation of the interval between intra-accumbens injection of apomorphine and the commencement of testing from 7 to 12, 17 and 22 min, respectively. Since no difference was found between locomotor activity of animals just placed in the novel environment and that of animals already present in this environment for one or more periods of record at fixed times after the injection, it is concluded that exploration does not contribute to locomotor hyperactivity induced by intra-accumbens injections of apomorphine.

Animals↗
PubMed1984

Clozapine--a serotonin antagonist?

The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.

Animals↗
PubMed1984

[Morphological changes in the neurons of the rat nucleus raphe dorsalis following application of 5,7-dihydroxytryptamine. A golgi-rapid-impregnation study].

The effect of stereotactically applicated 5,7-dihydroxytryptamine on the demonstrability of the different neuron types of the nucleus raphe dorsalis of the rat was investigated by means of the Golgi-rapid-impregnation technique. Degenerative changes could be demonstrated on the polygonal neurons, only. Typical variations of the dendritic structure was shown on the fusiform neurons. The pyriform neuron typ was not affected.

5,7-Dihydroxytryptamine↗
PubMed1983

An automated micropipet especially designed for use with the oil-well technique.

A high-precision microprocessor-controlled micropipetting unit which is applicable for serial enzyme or substrate microdeterminations with the oil-well technique is described. Positioning of the reaction wells, pipetting of microliter and submicroliter volumes, as well as measurements of incubation times are performed automatically following an adjustable present program.

Autoanalysis↗
PubMed1983

LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs.

The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms.

Animals↗
PubMed1983

Biochemistry of the ageing rat lens. I. Lens wet weight and lens dry weight with respect to sex differences.

The lens wet weight differed from the age of 136 days: the male lenses were significantly heavier than the female lenses. The dry weight, in percent of the lens wet and dry weight, of the water-soluble proteins decreased and the dry weight of the water-insoluble proteins increased during ageing. At an age of 870 days, when the dry weight curves crossed each other, the lens contains equal amounts of water-soluble and water-insoluble proteins. At the end of the life expectancy, the relation between the water-soluble and water-insoluble moiety was 0.7 for the rat and 3.5 for the bovine lens. The dry weight percent of the water-soluble proteins was lower for the female lens, whereas that of the water-insoluble proteins was higher for the female lens. The male lens, on the contrary, showed a higher percentage of water-soluble and a lower percentage of water-insoluble proteins with increasing age. The ratio R of the dry weight of water-soluble to water-insoluble proteins was, from the age of 429 days, lower for the female lens. During ageing, the proportion of the lens-water was higher for the male lens.

Age Factors↗
PubMed1980

Effects of atypical antidepressants on LSD potentiated apomorphine hypermotility in rats.

The model of LSD potentiated apomorphine hypermotility [5] was used to classify different atypical antidepressants (danitracen, mianserin, cyproheptadine) and pizotifen. All drugs have been shown to inhibit specifically the locomotor activity potentiating effect of LSD in a low dosage range (0.1-0.5 mg/kg i. p.) without influencing the apomorphine effect. Since there is some evidence that the effect of LSD is due to the inhibition of the activity of serotonergic raphe neurons, the marked antagonizing effects of danitracen, mainserin, cyproheptadine and pizotifen are regarded to be an expression of pronounced antiserotonin activity.

Animals↗
PubMed1979

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man.

In blind studies the effects of a new alpha-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.

Administration, Oral↗