In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism
SummaryUtilizing the cerebral microdialysis technique, we have compared in vivo the effects of selective MAO-A, MAO-B, and nonselective MAO inhibitors on striatal extracellular levels of dopamine (DA) and DA metabolites (DOPAC and HVA). The measurements were made in rats both under basal conditions and following L-DOPA administration. Extracellular levels of dopamine were enhanced and DA metabolite levels strongly inhibited both under basal conditions and following L-DOPA administration by pretreatment with the nonselective MAO inhibitor pargyline and the MAO-A selective inhibitors clorgyline and Ro 41-1049. The MAO-B inhi...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
CSF somatostatin increase in patients with early parkinsonian syndrome
SummarySomatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were determined in twenty-three patients with untreated parkinsonian syndrome (15 with Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at the moment of clinical diagnosis (mean duration of disease 1.1 ±0.2 years), and in 26 subjects without neurological symptoms. None of the IPD patients had a diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content was found to be significantly higher in patients with parkinsonian syndrome (107.9±9.8 pg/ml) than in control subjects (73.5± 8.4 pg/ml). Th...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Indoleamine concentrations in cerebrospinal fluid from patients with Alzheimer type and Binswanger type dementias before and after administration of citalopram, a synthetic serotonin uptake inhibitor
SummaryWe studied changes in the concentrations of serotonin (5-HT), kynurenine, and other indoleamines in the cerebrospinal fluid of patients with Alzheimer type dementia (ATD) and those with Binswanger type vascular dementia (VDBT), and changes in these indoleamine concentrations 2 weeks after administration of citalopram, a 5-HT uptake inhibitor. The concentrations of total 5-HT (p<0.005) and kynurenine (p<0.005) were significantly decreased in ATD patients in comparison to those of the controls. After citalopram administration, there was a remarkable increase in 5-HT concentration (249%, p<0.0001) and a signif...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Regional cerebral blood flow measured by 99m Tc-HMPAO SPECT differs in subgroups of Alzheimer's disease
In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity. (Source: Journal of Neural Transmission)
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Antiparkinsonian actions of glutamate antagonists — alone and with L-DOPA: A review of evidence and suggestions for possible mechanisms
SummaryThere has been much speculation of late as to whether antagonists of glutamate receptors can be used to combat the motor difficulties of Parkinson's disease, either as monotherapy, or as polytherapy to boost the effects of conventional L-DOPA treatment. The latter seems to be the more practical approach and the therapeutic implications of such treatment have been discussed in some detail. However, the mechanisms by which glutamate antagonists potentiate the antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have explored the evidence and considered the practicality of using NMDA and non-NMDA recep...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Lamotrigine in Parkinson's disease — a double blind study
SummaryAntiglutamatergic acting substances are considered to be useful tools for the treatment of hypokinesia in animal models for Parkinson's disease (PD). Moreover, most known antiglutamatergic compounds act postsynaptically and are either toxic or weak with regard to their clinical potency. The antiepileptic drug “Lamotrigine (LTG)” inhibits presynaptic glutamate release and may therefore provide a novel approach for PD therapy. Encouraging results from a pilot project led us to establish a placebo controlled trial including 20 patients with PD. The substance was generally well tolerated. There was a sig nificant di...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Free radical scavenging properties of apomorphine enantiomers and dopamine: Possible implication in their mechanism of action in parkinsonism
SummaryThe influence of R(-) apomorphine, S(+) apomorphine and deopamine on the oxidation kinetics of two polyunsaturated fatty acids (PUFA) (cholesteryl linoleate (CL) and Trilinolein (TL) was investigated The oxidation was initiated by free radicals generated through thermal decomposition of 2,2'-Azobis(2-methy-propionitrile) (AMPN) in phosphate buffer (pH 7.4) thermostated at 50 °C. The hydroperoxides formed were determined by iodine titration using a diode array spectrophotometer at 290 nm.Both enantiomers of apomorphine as well as dopamine exerted an inhibitory effect. Tocopherol ( α-tocopherol) and ascorbic acid we...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Monoamine oxidase A-inhibiting components of urinary tribulin: purification and identification
SummaryThe endogenous monoamine oxidase (MAO) inhibitory activity, termed tribulin, contains several components. We have previously identified one of them, isatin, which is a selective inhibitor of MAO B. In the present study we have purified several further components of human urinary tribulin which act as selective inhibitors of MAO A. They have been identified by gas chromatography-mass spectrometry (GC-MS) as ethyl indole-3-acetate (and/or methyl indole-3-propionate), methyl indole-3-acetate and ethyl 4-hydroxyphenylacetate. IC50 values for MAO A were found to be 44 μM (105 μM for methyl indole-3-propionate), 88 μM ...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Effect of age and disease duration on parkinsonian motor scores under levodopa therapy
SummaryOne hundred and fifty patients suffering from Parkinson's disease were analysed for the expression of the motor symptoms during optimum response to levodopa therapy (subscale III of the Unified Parkinson's Disease Rating Scale). Patients were grouped according to age ( ≤64, 65–74, ≥75 years). Disease duration and daily levodopa dosage were similar in the three groups. Pooled residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R) and distal motor impairment (DMI; hand and foot movements) increased with age (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than th...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Striatal [ 18 F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease
SummaryThe effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients t...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Modality dependent changes in event-related potentials correlate with specific cognitive functions in nondemented patients with Parkinson's disease
SummaryThe relationship between event-related potentials (ERPs) and cognitive functioning was studied in patients with Parkinson's Disease (PD) but without dementia. Auditory and visual stimuli were used; 30 subjects participated in the auditory study and 20 in the visual study. Patient groups did not differ with respect to gender, age, education, illness duration, and level of cognitive functioning. Visual stimuli were 2.3 cpd sinusoidal grating patterns randomly presented in an oddball paradigm (oblique vs. vertical spatial orientation). Auditory stimuli were tones presented at 70dB SPL at a rate of 1.1/second, also usin...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the striatum of MPTP-treated mice
SummaryThe expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was studied in the striatum of C57B1/6 mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP), which are used as a rodent model of Parkinson's disease (PD). Two weeks after systemic administration of MPTP (2 ×40 mg/kg, s.c. 18h apart), the lesion of the substantia nigra (SN) could be visualised by loss of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91% decrease in striatal dopamine levels. The levels of PENK and PDYN mRNAs were not significantly changed in the striatum of th e lesioned mice, as co...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats
SummaryThe present study investigated the effect of d-cycloserine, a partial agonist at the glycine binding site on NMDA receptor complex, on the performance of scopolamine-treated adult rats in a water maze task assessing spatial learning and in a delayed non-matching to position task assessing working memory in a spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.) impaired acquisition (increased escape latency and distance) and increased swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in acquisition performance but not the increases in behavioral activity. In the wor...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Effects of citalopram, a synthetic serotonin uptake inhibitor, on indoleamine and catecholamine concentrations in the cerebrospinal fluid of freely moving rats
SummaryWe studied changes in the concentrations of 5-hydroxytryptamine (5-HT), other indoleamines, and catecholamines in the cerebrospinal fluid (CSF) of freely-moving rats that had been administered citalopram, ±1-[3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzofurancarbonitrile hydrobromide), a selective inhibitor of 5-HT uptake. In a microdialysis experiment, the intracerebral extracellular free 5-HT increased significantly, peaking 60 to 90 min after citalopram (30 mg/kg p.o.) was a dministerd. The 5-HT concentrations in CSF from the cisterna magna increased significantly, reaching a maximum 6 hour...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
Human transplacental transfer of carbidopa/levodopa
SummaryA paucity of information is available concerning the use of levodopa and carbidopa during pregnancy. Particularly lacking is whether these agents cross the placenta and whether levodopa undergoes metabolism in the fetus. The present study carried out in aborted fetal tissues demonstrates that levodopa crosses the placental barrier and suggests that it may be metabolized in fetal tissues, including the brain and spinal cord. The possibility exists that early exposure to levodopa or dopamine may alter the normal neuronal development in the fetus, and caution in the use of levodopa during pregnancy should be observed. ...
Source: Journal of Neural Transmission - June 1, 1995 Category: Neurology Source Type: research
