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Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

At least 451 records · Page 25Linked to original sources
PubMed1985

Increased life expectancy resulting from addition of L-deprenyl to Madopar treatment in Parkinson's disease: a longterm study.

In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar alone (n = 377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n = 564) have been compared in Parkinsonian patients. In patients who lost their response to conventional Madopar therapy the addition of l-deprenyl resulted in a significant recouping of levodopa effect. The survival analysis revealed a significant increase of life expectancy in Madopar--l-deprenyl group regardless of the fact whether or not the significant demographic differences between the two groups were taken into account. Although the mechanism underlying this action of l-deprenyl is not known, the results are interpreted as indicating l-deprenyl's ability to prevent or retard the degeneration of striatal dopaminergic neurons. l-Deprenyl is the first anti-Parkinson drug having such a property. This hypothesis is not far fetched since l-deprenyl selectively prevents the degeneration of striatal dopaminergic neurons induced in animals by the illicit drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since latter compound is known to cause Parkinsonism in man and primates or Parkinson-like neurochemical and pathological changes in other animals the implications of the present study involving monoamine oxidase activity and l-deprenyl are apparent.

Adult↗
PubMed1985

Increased synaptic markers in hippocampus of depressed patients.

The neuronal adhesion molecule, D2-protein, and the marker for mature synapses, D3-protein, were studied by crossed immunoelectrophoresis in postmortem samples of human brain hippocampus and frontal cortex. The samples were obtained from 6 patients with endogenous depression, 6 patients with Parkinson's disease, and 9 controls without known neurological or psychiatric disorders. Both D2-protein and D3-protein were significantly increased in hippocampus of depressed patients compared to controls (32% and 30%, respectively) and compared to Parkinson's disease patients (31% and 24%, respectively). However, no significant change was observed in frontal cortex. Combined with the previously observed increase in the level of D2-like protein in blood plasma from depressed patients the findings may indicate that, at least in some regions of the brain, synaptic turnover is increased during depression.

Aged↗
PubMed1985

Comparison of benzodiazepine receptor binding in membranes from human or rat brain.

Specific high affinity binding of [3H]flunitrazepam to membranes from human brain was stimulated by gamma-aminobutyric acid (GABA), pentobarbital, 1-ethyl-4-(isopropylidene-hydrazino)-1H-pyrazolo[3,4b]pyridine-5-carboxy lic acid ethyl ester hydrochloride (SQ 20009) and avermectin B1a and was unaffected by 2 microM 4'-chlorodiazepam (Ro 5-4864) indicating that [3H]flunitrazepam in human brain as well as in rat brain predominantly binds to benzodiazepine receptors specific to brain, which was associated with a GABA receptor and several modulatory binding sites for drugs. The potency of several selective and non-selective ligands for benzodiazepine receptors for inhibition of the binding of [3H]flunitrazepam was compared in membranes from human or rat brain cerebellum, hippocampus and cerebral cortex. It was demonstrated that all these compounds, derived from different chemical structures, had a remarkably similar potency for inhibition of the binding of [3H]flunitrazepam in the corresponding regions of the human or rat brain. However, irreversible labelling of benzodiazepine binding sites with [3H]flunitrazepam and subsequent SDS-polyacrylamide gel electrophoresis and fluorography revealed more photolabelled protein bands in human than in rat cerebellum and hippocampus. The results seem to indicate that, although the pharmacological properties of reversible binding of [3H]flunitrazepam are remarkably similar in membranes from rat or human brain, the molecular heterogeneity of benzodiazepine binding sites is even greater in human than in rat brain.

Animals↗
PubMed1985

Neurochemical aspects of the Rett syndrome.

Preliminary biochemical analyses on plasma, urine, cerebrospinal fluid (CSF) and post mortem brain areas in the rare Rett syndrome indicate no gross disturbance of neurotransmitter function in the periphery. The amino acid pattern, the plasma catecholamines, dopamine, noradrenaline and adrenaline, serotonin in plasma and platelets, and monoamine oxidase (MAO) B-activity in platelets were not different from controls. Urinary metabolites of biogenic amines tended to be increased in the Rett syndrome. Amino acid and noradrenaline concentrations were not changed in lumbar CSF. In a single case of the Rett syndrome, lower values for most amino acids were notable in post-mortem human brain areas and this finding was accompanied by a severe reduction of dopamine, noradrenaline and serotonin, while the metabolite, DOPAC, most times is increased, and HVA and 5-HIAA are decreased. MAO activities, determined in four brain areas, showed no major abnormalities. 3H-spiroperidol binding was significantly below normal in the putamen and 3H tryptamine binding sites in the occipital cortex showed increased binding numbers with no changes in Hill-coefficients. In conclusion, our preliminary data indicate no severe changes in the peripheral neurotransmitter synthesis and turnover, while first post-mortem data indicate severe reduction of biogenic amine synthesis with enhanced turnover and reduced dopaminergic D-2 receptor activity in the advanced stage of a single case of the Rett syndrome.

Adolescent↗
PubMed1985

[Changes in and modulation of receptor activity in hepatic encephalopathy].

In hepatic encephalopathy (HE) brain uptake of large neutral amino acids is impaired with tryptophan crossing the blood brain barrier (BBB) to a much larger extent than all other competing amino acids (AA). The disturbance in the steady-state of transmitter is paralleled to the change of their kinetic data. This is reflected by an increase in serotonin (5-HT) synthesis and turnover, while the number of post-synaptic 5-HT1-binding sites is decreased, 5-HT2-receptor activity is dropping to a much smaller extent. On the other hand, presynaptic dopaminergic activity remains unchanged with no change in D2-receptor activity. Valine (VAL) improves the postsynaptic 5-HT function via modulating activity due to a regulatory mechanism at the membranal level in vitro and ex vivo. Furthermore, VAL leads to a significant reduction of serum ammonia (NH4+) and brain NH4+ concentration. VAL is able to antagonize the binding density diminishing effects of NH4+ on 5-HT binding sites. This effect could be characterized by the measurement of VAL binding sites being 5 to 10 fold higher than the number of leucin (LEU)-sites. Considering the chemical bonds involved in the attachment of biogenic amines and aminoacids (Schiff-bases equilibria) the modulating action of NH4+ on neural transmission may be clarified. Tryptamine can displace the postsynaptic binding of 5-HT in brain tissue and is a possible antagonist to physiological and pharmacological effects of 5-HT. The dynamic changes of the kinetic behaviour of tryptamine-binding might demonstrate a compensating effect as shown in an increase of tryptaminergic receptor activity. As a working hypothesis, the different relative strengths of electron-pair donor and -acceptor sites of both compounds are suggested to their complementary physiological interaction. GABA, an inhibitory transmitter of the CNS is diminished in its maximal binding capacity in severe HE and is independent of NH4+ influence. Furthermore, glutamate and aspartate-receptors decrease in experimentally induced hepatic coma. L-LEU shows modulating effects of glutamine binding. Glycin-activity is increased, while naloxone- and D-ala2-methionine-encephalinamid binding are not different from controls. These data demonstrate a different influence of various brain receptors and binding sites by HE and indicate a differentiated disturbance of (neuronal) membrane activity. Therefore disturbed interneuronal dynamics might be important pathophysiological mechanisms underlying hepatic coma.

Ammonia↗
PubMed1984

Bimodal distribution of dopamine receptor densities in brains of schizophrenics.

The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Antipsychotic Agents↗
PubMed1984

L-deprenyl plus L-phenylalanine in the treatment of depression.

The antidepressive efficacy of 1-deprenyl (5-10 mg daily) plus 1-phenylalanine (250 mg/day) has been evaluated in 155 unipolar depressed patients. Both oral and intravenous administration showed beneficial effects in 90% of outpatients and 80.5% of inpatients. It is concluded that this combined treatment has a potent antidepressive action based on the accumulation of 1-phenylethylamine in the brain.

Depressive Disorder↗
PubMed1983

Phenylethylamine and phenylacetic acid in CSF of schizophrenics and healthy controls.

Phenylethylamine (PEA) is an endogenous substance with amphetamine-like stimulant properties. On the basis of this ability an abnormal brain PEA metabolism has been proposed as an etiological factor in some forms of schizophrenia. In the present study 28 schizophrenic patients and 15 healthy controls were investigated. No significant difference from control values was found in PEA concentration in cerebrospinal fluid (CSF) of either untreated of neuroleptic-treated schizophrenics. However, 2 schizophrenics with highest BPRS scores had extremely high PES concentrations. Free phenylacetic acid (PAA), the major metabolite of PEA, was significantly decreased in ummedicated but not in drug-treated schizophrenics. Because of the assumed neuromodulatory properties of PEA, it is suggested that lowered PAA concentrations and the tendency for PEA to be elevated may imply that altered central neurotransmission occurs in certain forms of schizophrenia.

Adult↗
PubMed1983

DL-3,4-threo-DOPS in Parkinson's disease: effects on orthostatic hypotension and dizziness.

Parkinsonian patients with orthostatic hypotension and dizziness due to usual antiparkinson therapy have been treated with the precursor amino-acid of noradrenaline, DL-3,4-threo-dihydroxyphenylserine (DL-3,4-threo-DOPS). Oral and intravenous administration improved these side effects significantly. A combined treatment of L-dopa, peripheral decarboxylase inhibitor and DL-3,4-threo-DOPS seems to be of benefit with respect to akinesia and orthostatic hypotension.

Aged↗
PubMed1983

Dopamine and noradrenalin in the cerebrospinal fluid of schizophrenic patients.

Concentrations of both dopamine (DA) and noradrenalin (NA) were determined in the cerebrospinal fluid (CSF) of schizophrenic patients with and without neuroleptic treatment and in healthy controls. No significant differences were found between unmedicated patients and controls for either DA or NA. Patients receiving neuroleptics showed significantly higher levels of both DA and NA in the CSF. These results suggest that the reported findings of increased NA in the CSF and increased DA and NA in the brain of schizophrenic patients could be due, at least in part, to the effects of neuroleptic drugs.

Adult↗
PubMed1983

Neurochemical insights into monoamine oxidase inhibitors, with special reference to deprenyl (selegiline).

Monoamine oxidase (MAO) is distributed in neurons and non-neuronal tissue in the human central nervous system. It occurs there as MAO type A and MAO type B. It is not, however, established where both types are located intra- and/or extra-neuronally. Recently, the use of selective MAO-B blockers has shown beneficial effects in the treatment of Parkinson's disease (PD). Knowledge about the locus of action of MAO inhibitors is therefore of great importance. Our findings indicate that MAO-B inhibitors like deprenyl act by blocking neuronal and extra-neuronal MAO-B. This demonstrates that in the early stages of PD the action of deprenyl improves dopamine neurotransmission and hormonal action, whereas in the advanced stages of the disease, when there is progressive loss of dopaminergic neurons accompanied by gliosis, the drug seems to exert beneficial effects via the hormonal route.

Aged↗
PubMed1983

Studies on the neurotransmitter binding to pig brain microvessels.

Microvessels from pig brain areas were prepared by differential centrifugation techniques. These fractions were assayed for purity and structural unity by marker enzyme determination, light and electron microscopy. Binding properties of 3H-flunitrazepam were studied in different brain regions. Kinetic studies of 3H-flunitrazepam showed BMax-values of 0,42 +/- 0,3 pmol/mg protein and KD-values of 1,26 +/- 0,6 nM and were compared to a synaptosomal membrane fraction (P2-fraction) with BMax = 2,68 +/- 0,5 pmol/mg protein and a KD of 1,95 +/- 0,3 nM. GABA kinetic studies gave IC50-values of 250 nM in the microvessel fraction and 40 nM in the P2-fraction.

Animals↗