Search PubMed⌕ Search

Biomedical subjects

B Nickel

Publications and source records attributed to B Nickel.

At least 55 records · Page 3Linked to original sources
PubMed1989

Comparison of changes in the EEG of freely moving rats induced by enciprazine, buspirone and diazepam.

The effect of enciprazine, buspirone and diazepam was investigated on the cortical electrical activity in freely-moving rats. Enciprazine (5 mg/kg, i.p.) and buspirone (5 mg/kg, i.p.) induced comparable changes, consisting in decreases of mean power values in delta and theta and increases in alpha and beta EEG frequency bands. Regarding only a particular area of the brain or particular frequency bands, these two compounds could not be clearly separated from each other. Changes in frequency bands induced by O-methoxy-phenyl-piperazine (5 mg/kg i.p.) (D 15157), the presumed main metabolite of enciprazine, were dose-related to that caused by the parent compound. The second metabolite (R,S)-1-4-(1-methoxy-4-hydroxy-phenyl)piperazin-1-yl-3-(3,4,5- trimethoxyphenoxy)propan-2-ol-dihydrochloride (D 20092) (5 mg/kg i.p.) evoked only minimal changes in the different frequency bands of the rats. The power spectra did not significantly differ from those seen in animals treated with saline. The action of diazepam (2 mg/kg i.p.) was characterized by decreases in alpha and delta frequency bands, accompanied by marked increases in fast beta waves. The marked frequency shifts caused by buspirone and enciprazine could clearly be differentiated from the EEG changes evoked by the minor tranquilizer, diazepam.

Animals↗
PubMed1989

Mode of antinociceptive action of flupirtine in the rat.

1. Flupirtine is a novel, centrally acting, non-opioid analgesic agent. The present investigation was undertaken to ascertain which neuronal systems might be responsible for its antinociceptive effect in rodents. The antinociceptive responses to the test compounds were examined in the tail-flick test. 2. The selective destruction of noradrenergic pathways by 6-hydroxydopamine considerably reduced the flupirtine-induced inhibition of nociceptive responses but not the clonidine-induced antinociception which was significantly enhanced. Depletion of spinal 5-hydroxytryptaminergic pathways by pretreatment with 5,7-dihydroxytryptamine failed to affect the action of flupirtine and clonidine. 3. The depletion of neurotransmitters by reserpine totally abolished the antinociceptive action of flupirtine. By contrast, clonidine-induced inhibition of nociceptive responses remained unchanged. 4. Inhibition of the synthesis of noradrenaline by alpha-methyl-L-p-tyrosine attenuated the antinociception induced by flupirtine. In contrast, inhibition of the synthesis of 5-hydroxytryptamine by (+/-)-6-fluorotryptophan did not influence the antinociceptive activity of flupirtine. 5. Inhibition of noradrenaline uptake by imipramine led to a significant augmentation of flupirtine-induced antinociception. 6. Selective antagonists at alpha-adrenoceptors significantly decreased the antinociceptive action of flupirtine. Antinociception induced by clonidine was significantly diminished by idazoxan but not by prazosin. 7. The 5-hydroxytryptamine (5-HT) antagonist, ketanserin diminished the antinociceptive activity of flupirtine, probably due to its additional alpha 1-adrenoceptor antagonist activity. The antinociceptive effect of clonidine was not influenced by ketanserin. 8. Cholinoceptor antagonists such as mecamylamine and pirenzepine did not alter the antinociceptive action of flupirtine. Flupirtine-induced antinociception also remained unchanged after pretreatment with haloperidol. 9. Flupirtine has no pharmacologically relevant affinity for alpha 1-, alpha 2-adrenoceptors, 5-HT1- and 5-HT2-receptors as shown in direct binding studies. 10. The present results indicate that the antinociceptive action induced by flupirtine depends on the descending noradrenergic pain-modulating system.

Adrenergic alpha-Antagonists↗
PubMed1989

Dose- and time-dependent action of morphine, tramadol and flupirtine as studied by radioelectroencephalography in the freely behaving rat.

The necessity of testing psychoactive drugs in awake freely moving animals has led to the development of a telemetry-based system which enables the pharmacologist to follow centrally active molecules in their time- and dose-dependent effects on electric brain activity in terms of changes in spectral power density of extracellularly recorded field potentials (tele-EEG). This report describes the effect of three analgesics with respect to bioelectric changes in frontal cortex, thalamus, striatum and reticular formation. Two opiate drugs, morphine and tramadol, behaved very similarly despite a tenfold difference in dosage, whereas flupirtine, a nonopiate analgesic, changed the frequency content of the EEG signals in an entirely different manner. The frequency pattern produced by the opiates closely resembles that of centrally acting serotonin uptake inhibitors and thus is consistent with the view of a serotonergic prevalence of neurochemical interactions within the recorded brain areas. In contrast, the action of flupirtine obviously can be attributed to a clonidine-like effect on noradrenergic alpha 2-receptors. The results are discussed with respect to already known influences of these drugs on indoleaminergic and catecholaminergic transmission.

Aminopyridines↗
PubMed1989

Improvement of fine motoric movement control by elevated dosages of vitamin B1, B6, and B12 in target shooting.

Oral application of elevated dosages of vitamin B1, B6 and B12 have been found to improve target shooting in marksmen, recruited from a local pentathlon association, in two different studies. Study 1 was performed in an open controlled design, whereas in study 2 the group treated with B-vitamins was compared in a double-blind fashion with a placebo control group including 8 by 8 volunteers and 10 by 9 volunteers, respectively. The volunteers were randomly assigned to the groups. Performance quality was followed in both studies over a period of 8 weeks, while participants were continuously supplied with a combination of vitamins B1, B6 and B12 (Neurobion or Neurobion forte; E. Merck, Darmstadt, and Cascan, Wiesbaden, Germany). In both studies, marksmen in the vitamin-treated groups showed statistically significant, considerably improved firing accuracy as measured by the number of points achieved within a series of 20 shots at each examination. In study 2 the degree of improvement was linearly dependent on the duration of vitamin treatment, whereas the placebo-treated group, similar to the untreated control group in study 1, did not show any prominent change. Performance quality in marksmenship closely correlates with the magnitude of physiological tremor. Tremor can also be involved in the regulation quality of sensory-motor control systems. Thus, an improvement in firing accuracy as found in both studies is by the same token an improvement of fine motor control of slow movements, involving, for example, basal ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

[Electrolyte disorders, EEG changes and epileptic seizures in alcohol withdrawal delirium].

For 180 patients suffering alcohol-withdrawal induced delirium, electrolytic concentration in the serum of Na, K, Ca, and Mg was determined in the early withdrawal phase, and the electroencephalograms of 95 delirium patients evaluated in respect of local and diffuse changes and epileptic activity, and compared in delirium patients with and without initial seizures. Delirium patients who had initial seizures suffered significantly longer-lasting periods of delirium and significantly more frequent electrolytic changes in the form of hypomagnesemia and hypopotassemia (hypokalemia). There was no significant difference in the EEG changes. A temporary metabolic disorder in the initial phase of the two-phase withdrawal process should be assumed to be the cause of seizures during alcohol withdrawal, and the pathogenetic significance of hypomagnesemia and hypopotassemia should be taken into consideration.

Alcohol Withdrawal Delirium↗
PubMed1989

Basal activities of adenylate and guanylate cyclase in lymphocytes and platelets of alcoholics.

Basal activities of adenylate cyclase and guanylate cyclase were determined in lymphocytes and platelets of alcoholics with different severity of alcoholic withdrawal syndrome. Compared to controls, significant changes were found in the basal activities of adenylate and guanylate cyclase in all groups of patients. Adenylate cyclase activity in lymphocytes has a positive correlation to the severity of the clinical states. Although we found increased guanylate cyclase activities in lymphocytes and decreased activities in platelets compared to controls, similar values of activities were obtained in all groups of alcoholics independently of their clinical state.

Adenylyl Cyclases↗
PubMed1989

The influence of different formula diets and different pharmaceutical formulations on the systemic availability of paracetamol, gallbladder size, and plasma glucose.

The influence of two liquid formula diets on the systemic availability of paracetamol was investigated in 12 healthy normal volunteers using a liquid and a solid paracetamol dosage form. The diets contained the same balanced amounts, but different patterns of nutrients and different amounts of dietary fiber. Plasma glucose and gallbladder response to the standard meal were used as indicators of gastric emptying. Paracetamol plasma concentrations following application of the liquid dosage form also served as a marker for the gastroduodenal transport of liquid gastric contents. For the liquid dosage form, the plasma concentration time curves did not vary with diet composition. However, with the tablets, a differential effect was observed. Following coingestion with the fiber depleted diet, the rate of systemic availability was reduced more than with the liquid preparation. A further delay was obvious, when the tablets were combined with the meal enriched in dietary fiber. Plasma glucose and gallbladder response did not vary with diet composition. Variations of gastric emptying are unlikely to account for the variability of food effects. Consequently our results illustrate that an interaction of certain meal components with a particular drug dosage form determines the rate of intragastric release of the active compound. This could be shown due to a high standardization of nutrition by using liquid formula diets. Because of the variation of drug release, paracetamol cannot be used as a marker of gastric emptying without taking into account the vehicle necessary for drug application. In contrast to previous studies, our data provide evidence that even balanced test meals retard paracetamol absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1989

[Distribution and metabolism of azoxybenzene in the rat].

No sex differences could been shown after absorption and distribution of azoxybenzen in the rat. The highest level occur in the thyroid gland, the adrenals and in the fat tissues. The maximum level was reached 30 min. after application.

Animals↗
PubMed1989

[What does the neurologist expect from interventional neuroradiology?].

The methods of interventional radiology require interdisciplinary cooperation. For bioptic methods also a cooperative formulation of the diagnosis is important, while for the occlusion or dilatation of vessels the whole proceeding necessarily is cooperative. The pathophysiologic processes in partial or total ischaemia of the central nervous system can be treated only by a complex periinterventional therapy program carried out by an experienced neurologic intensive care team.

Cerebrovascular Disorders↗
PubMed1988

Possible involvement of noradrenergic descending pain-modulating pathways in the mode of antinociceptive action of flupirtine, a novel non-opioid analgesic.

These experimental studies were conducted to obtain information about the antinociceptive action of flupirtine within the central nervous system. Flupirtine dose-dependently increased pain threshold in the electrostimulated pain test in mice. Its antinociceptive activity was attenuated by simultaneous administration of the noradrenergic alpha 1/alpha 2-antagonist yohimbine and alpha 2-antagonist idazoxane. By contrast, the analgesia induced by codeine or morphine was not influenced by alpha 2-adrenergic antagonists at all. A striking resemblance could be observed in the pharmaco-EEG of freely moving rats treated with clonidine and flupirtine, respectively. The present results are consistent with the hypothesis that the noradrenergic descending pain-modulating system might be involved in the antinociceptive mode of action of flupirtine.

Aminopyridines↗
PubMed1988

Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat.

Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine. The mixed alpha-1/alpha-2 adrenergic agonist clonidine and the highly specific alpha-2 adrenergic agonist UK-14304, both partially and dose-dependently produced flupirtine appropriate responding. The mixed alpha-1/alpha-2 antagonist yohimbine and the highly specific alpha-2 antagonists idazoxan and L-654,284 all partially and dose-dependently antagonized flupirtine appropriate responding. Neither of the alpha-1 agonists phenylephrine or ST 587 produced flupirtine appropriate responding, nor did the alpha-1 antagonist prazosin antagonize flupirtine responding. It is concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms.

Adrenergic alpha-Agonists↗
PubMed1988

[New analgesically-active N'-acylated phenylpiperazines].

Synthesis and pharmacodynamic properties of new analgesic active N'-acylated phenylpiperazines are described. 1-(3-Cyclohexyl-1-oxo-propyl)-4-(2-ethoxyphenyl)-piperazine (D 16 120) possesses strong non-opiate antinociceptive activity showing high therapeutic margin with respect to undesired side effects and toxicity.

Analgesics↗
PubMed1988

A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor.

Two-dimensional gel electrophoresis of cultured human skin fibroblast lysates reveals a silver-stained "spot" of molecular mass 56 kilodaltons (kDa) and isoelectric point (pI) 6.7, occasionally as part of a doublet with a minor pI 6.5 partner. Its presence in each of 23 genital skin fibroblast strains (6 labium majus, 17 prepuce) and its absence in 30 of 32 control non-genital skin fibroblast strains accords with the 3-fold greater concentration of androgen-receptor activity in the former. However, the size and intensity of the spot do not change when cells are preincubated for 48 hours with 3 nM methyltrienolone (MT, a non-metabolizable androgen), and it is pulse-labeled with [35S]methionine to an autoradiographically equal extent, with or without incubation in 3 nM MT for 2 or 16 hours. Furthermore, the protein identified by the spot is found in the labium majus skin fibroblast strains from 2 of 12 unrelated subjects with complete androgen resistance due to negligible androgen-receptor activity, but it is absent from those of 2 others who have the same phenotype despite a normal level of qualitatively abnormal androgen-receptor activity. Hence, it is very unlikely to be an androgen-induced protein, and it cannot be a functional version of the androgen receptor itself. Its absence in 12 of 14 labium majus strains of subjects with complete androgen resistance, regardless of 5 alpha-reductase activities, indicates that it is neither a constitutive cytotypic marker of genital skin fibroblast differentiation nor a reflection of that enzyme. When intact prepuce fibroblasts are covalently labeled by photolysis with 50 nM [3H]MT, the only specific labeling detectable after two-dimensional electrophoresis is in the 6.7 and 6.5 pI doublet of the 56 kDa protein. Considering the sensitivity of silver staining and the incomplete concordance between the androgen-receptor activity of a strain and the size/intensity of its 6.7 pI/56 kDa spot on the gels, we postulate the latter to be a comparatively abundant androgen-binding protein that is causally related to the androgen receptor. The precise nature of this relation remains to be elucidated by use of novel immunologic and/or nucleic acid probes for this protein and for the mature androgen receptor. In any event, the presence or absence of the 6.7 pI/56 kDa protein in genital skin fibroblast lysates is a new marker of genetic heterogeneity within the class of complete androgen resistance.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1987

The antinociceptive activity of flupirtine: a structurally new analgesic.

The antinociceptive activity of flupirtine was measured in various test procedures predictive of analgesic activity. In the electrostimulated pain test in mice the oral ED50 for flupirtine was 25.7 mg/kg p.o. Thus, flupirtine was approximately 31.7 times more potent than paracetamol (ED50: 814 mg/kg p.o.) and as potent as pentazocine (ED50: 38.5 mg/kg p.o.). Morphine (ED50: 16.8 mg/kg p.o.) was 1.5 times and buprenorphine (ED50: 2.6 mg/kg p.o.) 9.9 times more potent than flupirtine. In the hot plate test (mice) flupirtine (ED50: 32 mg/kg p.o.) was approximately half as potent as morphine (ED50: 15.5 mg/kg p.o.). The oral and intravenous antinociceptive activity (ED50) of flupirtine in the electrical tooth pulp stimulation test in conscious dogs was 3.5 mg/kg p.o. and 0.7 mg/kg i.v. which was similar to that of pentazocine (ED50: 4.2 mg/kg p.o. and 0.5 mg/kg i.v.). Buprenorphine had, as expected, stronger antinociceptive activity (ED50: 1.0 mg/kg p.o. and 0.04 mg/kg i.v.). Fifteen minutes after oral administration of 40 mg/kg flupirtine, the pain threshold in the electrostimulated pain test was increased by 54%. The maximal antinociceptive effect was observed 30 minutes after dosing. The analgesia lasted at least 75 minutes. Codeine significantly elevated the pain threshold 15 minutes after dosing. Its maximal effect was also reached 30 min after application but the antinociceptive activity wore off earlier than after flupirtine. The intracerebroventricular and intrathecal administration of flupirtine also caused dose dependent antinociceptive activity in dose ranges which, when applied systematically, did not produce analgesia in rats. The antinociceptive activity of flupirtine was not abolished by naloxone whether given orally or by the intraventricular or intrathecal routes. In opiate receptor binding studies flupirtine had no affinity for mu, delta or kappa opiate receptors at the highest concentration used (10(-5) M). Whereas buprenorphine and tramadol showed a striking similarity in the pharmaco-electroencephalogram recorded from different parts of the brain (frontal cortex, thalamus, striatum and the mesencephalic reticular formation) of the freely moving rat, flupirtine was clearly different in action. It produced dose dependent increases in nearly all frequency bands but its effects were different from those of the minor tranquillizer diazepam and the anticonvulsant phenobarbitone. These findings show that the central antinociceptive activity of flupirtine is not based on an opiate mechanism and is not comparable with that of diazepam and phenobarbitone.

Aminopyridines↗
PubMed1987

Comparative physical dependence studies in rats with flupirtine and opiate receptor stimulating analgesics.

In physical dependence studies in rats the principle criterion was loss of body weight after withdrawal of the dependence producing drug. Other typical signs of withdrawal were also observed. In contrast to buprenorphine, codeine and tramadol, flupirtine caused no decrease in body weight and no other withdrawal symptoms. Flupirtine does not produce opiate type physical dependence.

Aminopyridines↗
PubMed1987

Clinico-neurophysiological correlations in chronic alcoholic Korsakoff patients.

A group of 29 patients with chronic alcoholic KORSAKOFF syndrome (KS) showed a cumulative increase in the interpeak latencies (IPL)I-II to I-VII of the brainstem auditory evoked potentials (BAEP), highest significance with IPL I-VI (p = 7.27 X 10(-6). The KORSAKOFF core group showed higher multiple correlation coefficients R for the IPL than the KS with additional deficiencies of cerebral performance. The BAEP should be used for recording subclinical patterns of brainstem lesions in risk patients with chronic alcoholism.

Alcohol Amnestic Disorder↗
PubMed1987

Pharmaco-electroencephalography in the rat as a method for characterization of different types of analgesics.

The central actions of flupirtine, pentazocine, paracetamol and acetylsalicylic acid (ASA) have been studied by quantitative analysis of cerebral field potentials from the cortical limb area and occipital cortex of the rat. Whereas pentazocine reduced the intensity of the alpha waves in a manner typical of opioids, flupirtine increased the power in this frequency band. Unlike flupirtine, pentazocine produced a clear increase in delta power. Paracetamol and ASA had no effect on the frequency bands in the various cortical areas. The results indicate that different types of drugs can be clearly separated with respect to their actions on cerebral field potentials.

Acetaminophen↗