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[Acute acoustic trauma. The therapeutic effect of bencyclan in a controlled clinical trial (author's transl)].

In a retrospective study 103 patients with acute acoustic trauma (AAT) were investigated. The control group (53 patients) was treated with Dextran 40 (10% solution), neurotrop vitamins and Betahistin. Bencyclan was administered additionally in the test group (50 patients). Statistical analysis of the audiometric data showed the following results: 1. Mean hearing levels of the test group showed better improvement of threshold shifts, if the therapy started within 2 days or after more than 10 days after the AAT. 2. Regression-and correlation coefficients, however, in a regression analysis of absolute hearing gains and hearing losses before therapy, did not indicate a substantial effect of Bencyclan. 3. Neither did statistical tests with relative hearing gains show any significant differences between test-and control groups. Consequently Bencyclan is not likely to have a positive effect in AAT, if it is administered in the above mentioned way.

Adolescent↗

[Cardiac output and central-hemodynamic parameter under bencyclan (author's transl)].

In 17 patients with peripheral arterial occlusive disease the influence of intra-veinously applicated Bencyclane (Fludilat) on cardiac output and central-hemodynamic parameter has been investigated. While 100 mg (n = 8) of Bencyclane almost do not influence cardiac output, 200 mg (n = 9) cause a significant decrease of minute-volume of the heart by-17.22% and of heartfrequency by-8.85%. With either dose there is also a significant increase of aortic pressure, pulmonary arterial pressure and pulmonary vessel resistance to be seen. These results correlate with the animal-experimental proof of a negative inotropy under Bencyclane, and they have to be considered in therapeutical use.

Arterial Occlusive Diseases↗

Action of bencyclane-hydrogen-fumarate on the carbohydrate metabolism of bovine lens homogenates.

1-Benzyl-1-(3-dimethylaminopropoxy)cycloheptane (bencyclane-hydrogen-fumarate; Fludilat) in a concentration of 10-2 M effects an increase in the O2 consumption and the formation of CO2 in a 10% bovine lens homogenate. This effect is even increased if the glucose-substrate supply is raised from 25 mM to 37 mM. Investigations on the concentrations at ATP, ADP and AMP show that bencyclane is able to stabilize the physiologic distribution pattern of the three free adenine nucleotides. Further, the observed changes in the distribution pattern indicated that the fumaric acid rest of bencyclane may serve as a substrate for this reaction in the same way as fumarate.

Adenosine Diphosphate↗

[Bencyclan (Fludilat) in the treatment of patients with ischaemic cerebral infarction (author's transl)].

In 50 patients suffering from local cerebral circulation disturbances the effects of bencyclan--administered intravenously in a dosis of 500 mg per day--were evaluated under double-blind conditions. At the same time all patients received digitalis and physiotherapy. Besides a detailed recording of the neurological and psychopathological status a number of psychological tests were applied in order to get objective data about psychomotor function, cerebro-organic capacity and mood. The control recordings after a three weeks' treatment demonstrated an improvement of the clinical as well as the psychological parameters in either group. There were no marked, statistically significant differences in the extent of improvement between the bencyclan and the placebo group; that means bencyclan has no effect on the signs of ischaemic cerebrovascular disease, which exceeds the effects of digitalis and physiotherapy.

Adult↗

[Cardiac side-effects of bencyclan].

Bencyclan (Fludilat), used therapeutically as a vasodilator drug, exerts a distinct negative inotropic and chronotropic action on myocardium, in contrast to papaverine. It prolongs the functional refractory period in the isolated heart preparation. In isolated myocardial mitochondria it decreases the velocity of oxidative phosphorylation and the rate of calcium uptake. These results indicate that heart function should be checked if bencyclan is applied at high dosage, especially if other cardio-depressive substances such as narcotics, antidepressive and antiarrhythmic agents as well as beta-adrenergic blockers are used at the same time. On the other hand, the results suggest that bencyclan should be tested for possible use in the treatment of ischaemic heart disease as well as ventricular and supraventricular tachycardia.

Adrenergic beta-Antagonists↗

[Decrease of disaccharidase activity following application of bencyclan-hydrogenfumarate (author's transl)].

The disaccharidase activity of the small bowel mucosa of the rat is decreased by intraperitoneal application of Bencyclan-hydrogenfumarate. The doses applied were 10, 50 and 100 mg/kg body weight. The decrease rate after 100 mg/kg attained up to 50% of the control values. Furthermore, a reduction of villous height and an increase of the crypt depth has been observed in correlation with the enzyme activity decrease. Though functional and morphological alterations show a correlation, they cannot be explained by an antimetabolic-like effect because of the fact that the enzyme function recovers 72 h after application of the drug. Whilst our results do not sustain a cytostatic effect of Bencyclan-hydrogenfumarate, there is no doubt that the intraperitoneally applied drug influences the disaccharidase activity. These facts have to be considered in clinical therapy.

Animals↗

Determination of bencyclane in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of bencyclane in human plasma is presented. Bencyclane was extracted from human plasma with two 3-ml volumes of isooctane and was shaken for 10 min. The organic phase was separated and evaporated to dryness at 40 degrees C under a nitrogen stream. The residue was dissolved and an aliquot was injected into the gas chromatograph. The separation was performed with a DB-17 column with helium as the carrier gas. Nitrogen-selective detection was performed. The quantification was performed with the signal output. The limit of detection was 1 ng/ml.

Bencyclane↗

Interference of bencyclan with 11-hydroxycorticosteroids determinations.

Falsely high fluorimetric readings were obtained in plasma and urine 11-hydroxycorticosteroids (mostly cortisol) assays during the administration of bencyclan to hypertensive patients. No valid conclusion can be drawn from 11-hydroxycorticosteroids assays in bencyclan treated patients.

11-Hydroxycorticosteroids↗

Effects of papaverine, chloracyzine, and bencyclane on local blood flow and oxygen tension in cat brain.

In experiments on 100 cats with multichannel recording, the effects of three vasodilators - papaverine, chloracyzine, and bencyclane (Halidor) - on the volume velocity of the blood flow (by microthermistor technique) and on oxygen tension (by polarography) in the carotid artery, the cerebral cortex, the thalamus, and in white matter were tested. Considerable differences were found in the effects of the drugs mentioned, although all of them augment the total and local blood flow in the brain, and in most instances elevate the oxygen tension in arterial blood and cerebral tissue. Characteristic of papaverine is a uniform augmentation of blood supply to the cerebral cortex, the thalamus, and white matter, whereas chloracyzine, and especially bencyclane, primarily augment the blood supply to the cerebral cortex. In an analogous way the drugs tested influence the cerebral blood flow and oxygen tension in experimental cerebral ischaemia induced by intracarotid infusion of a serotonin solution.

Animals↗

[The effects of elevated calcium concentrations in artificial cerebrospinal fluid on pial arteries during perivascular microperfusion and the Ca++-antagonistic effect of bencyclane (author's transl)].

The influence of artificial cerebrospinal fluid (CSF) containing 6, 9 and 18 mEq/l Ca++, respectively, on 145 pial arteries of nine anesthetized cats was investigated by the perivascular microperfusion technique. The higher the concentration of Ca++ in the perivascular space and the longer these high Ca++ concentrations acted on the vascular wall, the more pronounced were the constrictions of the arteries. If N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine (bencyclane-hydrogenfumarate, Fludilat) (10 mg/100 ml) was added to the CSF, dilatations occurred, even if the concentrations of Ca++ were higher than in normal CSF (3 meq/l). The degree of dilatation, however, was dependent on the Ca++ concentration in the CSF. With high Ca++ in the CSF the dilatatory action of bencyclane was inhibited when K+ and H+ in the CSF were kept constant. The reaction can be described as Ca++ antagonism, the possible mechanisms of which are discussed.

Animals↗

[The effect of bencyclane, flunarizine and naftidrofuryl on a calorically induced long time nystagmus (author's transl)].

The method of a calorically induced long time stimulation is shown. Appr. 15 minutes after begin fo stimulation a nystagmus plateau can be observed. We used this plateau to demonstrate the effects of three cerebral vasoactive drugs--Bencyclane, Flunarizine and Naftidrofuryl-Hydrogenoxalate in a randomized double blind study. All of them depressed the nystagmus significantly. Naftidrofuryl by 38.4 +/- 4.6%, Flunarizine by 31 +/- 4.5% and Bencyclane by 25.1 +/- 3.8%. The depressing mechanism of Flunarizine is partly due to sedation.

Adult↗

Effects of bencyclane on concussion following head injury in mice.

Bencyclane showed a dose-dependent anti-concussive effect with a duration of at least 60 minutes in an experimental model of concussion induced by head injury. This long-lasting effect cannot be explained only by the changes in the serum level of the agent or the increase in brain circulation due to its vasodilative action, both of which are of much shorter durations. Our findings suggest that bencyclane causes alterations in brain metabolism, which is partly responsible for reduction in the duration of the experimental concussion.

Animals↗

[Bencyclan's effects "in vitro" on fibrinolysis (author's transl)].

The eventual fibrinolytic activity of Bencyclan (N-3-(1-benzil-cicloeptil-ossi)-propil-N-N-dimetil-amino-fumarato-acid) has been studied in vitro. The presence of eventuals FDP has been calculated through the Staphylococcal clumping test (SCT), by previous incubation of blood-samples with scalar concentrations of Bencyclan. No increase in the fibrinolytic activity with regard to the incubation of samples with the above-mentioned substance has been noticed.

Bencyclane↗

Neurogenic component in the effect of papaverine, drotaverine and bencyclane.

Papaverine, drotaverine and bencyclane, drugs considered to have direct action on the smooth muscle, inhibited synaptic transmission in the isolated a sympathetic ganglion of the frog. Their effect depended upon the concentration applied. The ganglionic blocking effect of papaverine and drotaverine in the concentration range from 10(-8) to 10(-6) mol/l was partially antagonized by naloxone and nalorphine as well as by increasing the Ca2+ concentration in the incubation medium. This refers to an activation of specific opiate receptors in the mechanism of ganglionic action of these drugs. The ganglionic effect of bencyclane may be due to its local anaesthetic property, since it was prevented by neither naloxone nor nalorphine, and an increase in the Ca2+ concentration in the medium had no influence on it.

Animals↗

[Bencyclane in memory disorders. Treatment of memory disorders caused by electroshock in a group of depressed patients].

Subjects treated with electroshock and subjected simultaneously to bencyclan at a dose of 00 mg (2 ampoules) i.v. and 100 mg (1 pill) per os pro die did not present dysmnesia either during the intervals between one electroshock treatment and another, nor at the conclusion of treatment (on average 12 sessions in about 40 days), while a control group treated at the same rhythm and with the same number of sessions, but without bencyclan, presented considerable memory lapses which disappeared only after a lengthy period of this latter treatment. Memory disturbances have been evaluated with a memorization test to which all patients were subjected. This test belongs to the group of intellectual efficiency reactive tests used in the psychology laboratory of the Catholic University of Milan; it consists of a group of 12 figures of common objects which, once observed, have to be recalled exactly immediately and some time later by the patient, who has to indicate the name and position of the objects represented in the chart.

Adult↗

[Combination of physiotherapeutic exercise therapy with bencyclane in intermittent claudication (author's transl)].

Earlier investigations had shown that an intensive physiotherapy program with 30 treatments in 6 weeks was the most rational therapy for intermittent claudication, but the question whether the therapeutic success could be improved by the addition of "vasoactive" substances remained open. For this reason, bencyclane was added to the basic physiotherapy in a double blind trial involving 109 ambulant patients. 91 or these were evaluated. The treatment group (n = 45) showed a greater increase in walking distance of 21.7% compared with the placebo group (n = 46). Also in the evaluation of the therapeutic success rate, the treatment group showed better results (84.4%) than the placebo group (71.7%). From this it can be concluded that the basic physiotherapy can be effectively supported with bencyclane.

Adult↗

[Effect of bencyclan and theophylline on changes of platelet aggregation and factor 3 activity].

The ADP- and adrenaline-induced platelet aggregation and platelet factor 3 availability were studied in patients before and eight hours after intravenous administration of bencyclan (100 mg) and/or theophylline (240 mg). Aggregation was primarily inhibited by bencyclan, the availability of factor 3 was inhibited by theophylline. Combination of both drugs exerted additive effects on both parameters. The combined use of drugs as inhibitors of aggregation is recommended, since they inhibit primary haemostasis simultaneously at two points of attack.

Bencyclane↗