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C H Gleiter

Publications and source records attributed to C H Gleiter.

At least 55 records · Page 3Linked to original sources
PubMed1998

Influence of urine pH and urinary flow on the renal excretion of memantine.

AIMS: The present study assessed the influence of urinary flow rate and urine pH on the renal excretion of the NMDA-receptor antagonist memantine. METHODS: In a randomized, open, four-period cross-over trial, 12 healthy male volunteers received 10 mg memantine daily for 43 days. After reaching steady state conditions the volunteers were allocated to four different regimens to alter urine pH and urinary flow, which were each separated by a 1 week period while the study medication continued (A: acidification of urine pH, low urinary flow; B: acidification of urine pH, high urinary flow; C: alkalinization of urine pH, low urinary flow; D: alkalinization of urine pH, high urinary flow). RESULTS: The renal clearance of memantine (CL(R)) in regimen A and B was 7-10 fold higher in comparison with regimen C and D (P<0.05). There were small but statistically significant differences of CL(R) between the two regimens with acidic urine pH (A: median: 210.2 ml min(-1) vs B: median: 218.7 ml min(-1)) and between the two regimens with alkaline urine pH (C: median: 19.4 ml min(-1) vs D: median: 30.5 ml min(-1)). The amount of memantine excreted into the urine within one regimen (Ae0-24h) was 5.7-7.4 fold higher in regimens A and B than C and D (P< 0.05). Differences of the AUC(0,24 h) and Cmax/AUC(0,24 h) were significant (P<0.05) between each of the regimens with acidic urine pH (A, B) and regimens (C, D) with alkaline urine pH (A vs C, A vs D, B vs C, B vs D) but not between regimens A vs B or C vs D. CONCLUSIONS: The present study demonstrated a considerable effect of urine pH, whereas no clinically relevant change of the renal excretion of memantine with urinary flow could be detected. As the renal excretion of memantine may have an impact on therapeutic efficacy changes of dietary habits that may alter urine pH should be avoided during treatment with memantine.

Adult↗
PubMed1998

Monoamine oxidase inhibitors. A perspective on their use in the elderly.

Monoamine oxidase inhibitors (MAOIs) are mainly used in psychiatry for the treatment of depressive disorders and in neurology for the treatment of Parkinson's disease. While the classical, nonselective and nonreversible MAOIs, such as phenelzine and tranylcypromine, are characterised by the risk of inducing a hypertensive crisis when dietary tyramine is ingested, the selective monoamine oxidase-B (MAO-B) inhibitor selegiline (deprenyl) and, even more so, the selective and reversible monoamine oxidase-A (MAO-A) inhibitor moclobemide, are free from this potential interaction. Drug tolerability data for the elderly show that moclobemide is one of the most well tolerated compounds. Selegiline, especially when used in combination with levodopa, can cause anorexia, dry mouth, dyskinesia and, most problematic, orthostatic hypotension. For the traditional MAOIs, phenelzine and tranylcypromine, published data are insufficient to be able to give a conclusive tolerability statement regarding the use of these compounds in elderly people. Although orthostatic hypotension occurs in most patients treated with traditional MAOIs, the incidence in elderly patients with depression does not appear to be greater than that reported with tricyclic antidepressants.

Aged↗
PubMed1997

[Fluoxetine].

Explore the source record for details and available documents.

Animals↗
PubMed1997

Renal response to infusion of dopamine precursors in anaesthetized rats.

In the present study the renal response to intravenous infusion of the catecholamine precursors L-dihydroxyphenylalanine (L-DOPA) or L-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (U(DA)V) by HPLC and sodium excretion (U(Na)V) by flame photometry. We found that basal U(DA)V was 6.5 +/- 0.5 pmol/min per 100 g body weight (mean +/- SEM). Intravenous infusion of L-tyrosine at 0. 1-3.0 micromol/min dose dependently enhanced U(DA)V (17 +/- 3 to 144 +/- 14 pmol/min respectively) with higher doses of L-tyrosine resulting in no further increase in U(DA)V. Compared with L-tyrosine administration significantly lower doses of L-DOPA (0.07 to 35 nmol/min) caused increases in U(DA)V which were orders of magnitude higher (18 +/- 1 to 7800 +/- 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to L-tyrosine or L-DOPA infusion. No variations in urinary flow rate or in U(Na)V could be observed which were significantly correlated to changes in U(DA)V. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 +/- 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of L-DOPA. The unchanged GFR and U(Na)V in spite of large variations of U(DA)V argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma.

Adrenal Glands↗
PubMed1997

Non-response to maprotiline caused by ultra-rapid metabolism that is different from CYP2D6?

CASE: We are reporting about a patient with major depression who failed to respond to pharmacotherapy due to ultra-rapid metabolism of maprotiline. Under daily oral doses of 175 mg maprotiline, the patient's metabolic ratio (MR) for maprotiline in plasma was 9.2 (expected MRp: 2.4) and the clearance of maprotiline (CLM) was 4190 ml.min-1 (expected CLM = 1220 in extensive metabolisers of CYP2D6). RESULTS: The patient's MRurine for sparteine was 0.5, which is within the range for extensive metabolisers of CYP2D6. Genotyping did not show a duplication of the CYP2D6L allele. The patient's caffeine half-life was 10 h, thus, precluding ultra-rapid metabolism for CYP1A2. The therapeutic regiment was changed to co-administration of 200 mg maprotiline and 20 mg fluoxetine once per day in order to inhibit metabolism via CYP2D6. Subsequently, MRP of maprotiline (4.9) and CLM were reduced (1900 ml.min-1; expected CLM in poor metabolisers: of CYP2D6 364). This regimen improved the clinical outcome of the underlying disease. CONCLUSION: We conclude that for the non-response seen with maprotiline, P450 isozymes other than CYP2D6 or CYP1A2 are responsible. As CYP2C19 is involved in the metabolism of a number of tricyclic antidepressants it may be a candidate for ultra-rapid metabolism in this patient.

Alleles↗
PubMed1997

Dexamethasone down-regulates the expression of L-selectin on the surface of neutrophils and lymphocytes in humans.

OBJECTIVE: On the basis of previous animal studies, we hypothesized that dexamethasone may reduce the expression of L-selectin on neutrophils and lymphocytes in healthy men. METHODS: A double-blind, randomized, placebo-controlled, and three-way crossover trial was conducted in nine healthy men. Every subject received four identical infusions of saline solution, 0.04 mg/kg dexamethasone, or 1.0 mg/kg dexamethasone during three observation periods of 48 hours each. RESULTS: Dexamethasone time and dose dependently decreased the L-selectin expression on neutrophils and lymphocytes as measured by flowcytometry. This effect occurred with a time lag of 8 hours after start of treatment: the L-selectin binding index of neutrophils decreased by a maximum of -50% (confidence interval [CI], -37% to -63%) and that of lymphocytes by -26% (CI, -8% to -45%) at 32 hours after the start of treatment with high-dose dexamethasone (p < 0.016). Low-dose dexamethasone had only a transient effect on L-selectin expression of lymphocytes and a less pronounced effect on L-selectin expression of neutrophils. CONCLUSION: Dexamethasone time and dose dependently decreases L-selectin expression on neutrophils and lymphocytes in health men, an effect that is less pronounced than that previously reported for animals.

Adult↗
PubMed1997

Fenoterol but not dobutamine increases erythropoietin production in humans.

OBJECTIVE: This study assessed the role of adrenergic signal transmission in the control of renal erythropoietin (EPO) production in humans. METHODS: Forty-six healthy male volunteers underwent a hemorrhage of 750 ml. After phlebotomy, they received (intravenously for 6 hours in a parallel, randomized, placebo-controlled and single-blind design) either placebo (0.9% sodium chloride), or the beta 2-adrenergic receptor agonist fenoterol (1.5 microgram/min), or the beta 1-adrenergic receptor agonist dobutamine (5 micrograms/kg/min), or the nonselective beta-adrenergic receptor antagonist propranolol (loading dose of 0.14 mg/kg over 20 minutes, followed by 0.63 micrograms/kg/min). RESULTS: The AUCEPO(0-48 hr)fenoterol was 37% higher (p < 0.03) than AUCEPO(0-48 hr)placebo, whereas AUCEPO(0-48 hr)dobutamine and AUCEPO(0-48 hr)propranolol were comparable with placebo. Creatinine clearance was significantly increased during dobutamine treatment. Urinary cyclic adenosine monophosphate excretion was increased only by fenoterol treatment, whereas serum potassium levels were decreased. Plasma renin activity was significantly increased during dobutamine and fenoterol infusion. CONCLUSIONS: This study shows in a model of controlled, physiologic stimulation of renal erythropoietin production that the beta 2-adrenergic receptor agonist fenoterol but not the beta 1-adrenergic receptor agonist dobutamine is able to increase erythropoietin levels in humans. The result can be interpreted as a hint that signals for the control of erythropoietin production may be mediated by beta 2-adrenergic receptors rather than by beta 1-adrenergic receptors. It appears to be unlikely that an increase of renin concentrations or glomerular filtration rate is causally linked to the control of erythropoietin production in this experimental setting.

Adrenergic beta-Agonists↗
PubMed1997

Brofaromine versus imipramine in in-patients with major depression--a controlled trial.

Brofaromine is a selective and reversible inhibitor of monoamine oxidase A. The efficacy and safety of this compound as compared with tricyclic antidepressants, classical monoamine oxidase inhibitors and placebo has been demonstrated in several clinical trials. The present 6-week, double-blind, randomized trial compared brofaromine with imipramine in in-patients with major depression. Brofaromine was as effective as imipramine in the treatment of major depression, but exhibited a different side-effect profile, in particular lacking the anticholinergic and certain cardiovascular side-effects of the tricyclic imipramine, but more likely to induce sleep disturbances. In this study, in-patients were examined, since the majority of controlled clinical trials on depressed patients conducted so far have focused on the evaluation of out-patients. If one assumes that a different degree of severity of depression exists between these two patient groups, then the results of those trials conducted on out-patients cannot readily be transferred to in-patients.

Adolescent↗
PubMed1997

Evidence against a major role of adenosine in oxygen-dependent regulation of erythropoietin in rats.

This in vivo study investigated whether adenosine (ADO) plays a role in oxygen-dependent production of erythropoietin (EPO). Exposure of rats to 0.075% carbon monoxide (CO) for four hours was used as a stimulus for EPO production. To inhibit potential effects of ADO, rats were treated with the non-specific ADO antagonist theophylline, the selective ADO A1 receptor blockers DPCPX and KW-3902, the selective ADO A2 receptor blocker DMPX, and AOPCP, an inhibitor of 5'-ectonucleotidase, an ADO generating enzyme that is expressed on the surface of EPO producing cells. To stimulate ADO receptor activity, animals were treated with the selective ADO A1 and A2 receptor agonists CHA and CGS 21680, the ADO reuptake inhibitors dipyridamole and soluflazine and the ADO desaminase inhibitor EHNA. At doses known to interfere with ADO signal transmission in vivo, none of these substances either influenced EPO serum levels in normoxic rats or affected the approximately 30-fold rise in EPO serum levels and the increase in renal EPO mRNA after exposure to carbon monoxide. Continuous administration of theophylline to normoxic rats for seven days did not alter hematocrit, hemoglobin or EPO serum levels. Taken together, these experiments do not support the hypothesis that ADO plays an important role in the regulation of EPO production.

Adenine↗
PubMed1997

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine.

AIMS: Objective of this study was to investigate whether adenosine modulates renal erythropoietin production. METHODS: In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000 m in a low pressure chamber for 5.5 h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo. RESULTS: Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations. CONCLUSIONS: The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.

Adenosine↗
PubMed1996

Pharmacokinetics of CGP 36,742, an orally active GABAB antagonist, in humans.

A study was conducted to evaluate the pharmacokinetics of CGP 36 742 (3-aminopropyl-n-butyl-phosphinic acid), an orally active gamma-aminobutyric acid B (GABAB) antagonist, in humans. Pharmacokinetic results after a single oral (600 mg) dose included maximum observed concentration (Cmax), 27 mumol/L (95% CI 22.9, 30.8); time to Cmax (tmax), 3 hours (median); half-life (t1/2), 3.6 hours (95% CI 3.24, 3.9); renal clearance (ClR), 125 mL/min (95% CI 114, 136); and absolute bioavailability (Fabs), 0.44 (95% CI 0.33, 0.47). Administration with food decreased the oral systemic availability (Frel) by 30%. The volume of distribution (285 L/kg) was in the order of magnitude of extracellular body water. The absorbed fraction of the compound was excreted completely and unchanged via the kidney, thus renal function would be the limiting factor for excretion. The rate of absorption and amount absorbed did not differ significantly between elderly and young healthy male volunteers, both after single and multiple doses. There was no gender-related difference in pharmacokinetics in healthy elderly volunteers. CGP 36 742 showed an excellent safety profile: there were no clinically relevant changes in cardiovascular variables, body temperature, or blood chemistry. In the placebo-controlled trial, adverse experiences were rare and evenly distributed among participants receiving placebo and the study drug. In addition, a newly developed high-performance liquid chromatography (HPLC) method for measurement of CGP 36 742 concentrations in plasma and urine using fluorescence detection is described.

Administration, Oral↗
PubMed1996

Brofaromine--a review of its pharmacological properties and therapeutic use.

The antidepressant activity of monoamine oxidase inhibitors has been well established for 30 years. Nevertheless, this group of compounds was handled with great care, mainly because of the interaction potential with tyramine-containing foodstuff. With the discovery of reversible and selective inhibitors of monoamine oxidase type A a renaissance of these compounds has begun. In this paper one of these new substances--brofaromine--will be described in detail. Biochemical and pharmacological aspects will be reviewed, showing that brofaromine is a selective and reversible inhibitor of monoamine oxidase type A with additional serotonin reuptake inhibiting properties. Both mechanisms of action may synergize in the antidepressant effect of the compound. The main results of clinical trials in depression and other indication areas will also be covered. Special attention will be put on the side effect profile.

Animals↗
PubMed1996

Erythropoietin production in healthy volunteers subjected to controlled haemorrhage: evidence against a major role for adenosine.

1. This study was carried out to assess the role of adenosine in the regulation of human erythropoietin (EPO) production. To this end we investigated in healthy volunteers whether the nonspecific adenosine antagonist theophylline increases and the adenosine uptake inhibitor dipyridamole decreases EPO production in response to an haemorrhage of 750 ml. 2. Healthy male nonsmokers received i.v. in a parallel, randomized, single-blind trial theophylline (loading dose 5 mg kg-1 over 20 min, followed by 0.5 mg kg-1 min-1), dipyridamole (0.21 mg kg-1 h-1) or placebo (0.9% NaCl) for 6 h following the phlebotomy. EPO concentrations were followed up to 72 h after phlebotomy. 3. Following blood loss EPO concentrations increased during all treatments. The AUCEPO (0,72 h) were not statistically significantly different (theophylline: 398 +/- 30, dipyridamole: 301 +/- 15, placebo: 332 +/- 57 [mu ml-1 h]). Creatinine clearance and urinary cAMP excretion were unaltered by any treatment. Urinary excretion of adenosine was significantly increased during infusion of dipyridamole. Plasma renin activity was significantly increased during theophylline infusion. 4. In our model of controlled, physiological stimulation of EPO production by haemorrhage, adenosine appears unlikely to play a major role as a mediator of renal EPO production.

Adenosine↗
PubMed1996

Adverse CNS-effects of beta-adrenoceptor blockers.

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Adrenergic beta-Antagonists↗