Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behaviour of some urinary metabolites of tryptophan/nicotinic acid pathway was studied in 7 patients with Parkinson's disease during a 24-day period of levodopa treatment. Corresponding to the appearance of side-effects (agitation, anorexia, dysphagia, glossitis, abdominal pains) in 5 patients there was an increase in urinary Ky, AA, AAG, o-AHA, and 3-HK, while 3-HAA excretion fell. Since no other drugs were given, it was presumed that this effect was due to levodopa administration.
 ...
PMID:Tryptophan/nicotinic acid pathway during levodopa treatment of Parkinsonism. 124 93

Clinical and experimental evidence suggests that degeneration of the locus coeruleus (LC) may be responsible for certain symptoms of Parkinson's disease (PD). We have, therefore, studied the effects of LC lesion on dopamine (DA) metabolism in the rat striatum. Unilateral depletion of norepinephrine (NE) was obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the dorsal NE bundle (DNEB). Rats were sacrificed 1 or 3 weeks after lesioning. 6-OHDA induced approximately 50% depletion of NE in the ipsilateral hippocampus at 1 week postinjection, and over 75% depletion after 3 weeks. DNEB lesions had no effect on DA or DOPAC levels in the ipsi- or contralateral striatum at either time point. Lesions also failed to affect DA synthesis or utilization in either striatum. The metabolism of exogenous levodopa in the striatum was also unaffected. It is suggested that any possible effect of the LC on DA transmission in the striatum is not mediated by the DNEB.
 ...
PMID:The locus coeruleus and dopaminergic function in rat brain: implications to parkinsonism. 161 53

Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40-7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine), were also increased by Ro 40-7592. The drug stimulated exploratory activity in the open field test. It decreased the levels of HVA and 3-MT, increased the level of DOPAC but did not change the levels of dopamine in the striatum, nucleus accumbens and frontal cortex. These results indicate that Ro 40-7592 may improve the therapy with L-DOPA (plus decarboxylase inhibitor) of Parkinson's disease.
 ...
PMID:Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease. 197 8

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.
 ...
PMID:L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease. 210 91

We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity.
 ...
PMID:GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice. 225 Jan 72

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.
 ...
PMID:Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. 230 73

We evaluated neurochemically, behaviorally, and neuropathologically the availability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black (BL) mice as a model for Parkinson's disease. The dopamine and 3,4-dihydroxyphenyl acetic acid content in the striatum, measured by high-performance liquid chromatography with an electrochemical detector, decreased by 70% at 10 and 20 days after the withdrawal of MPTP (30 mg/kg, i.p. twice daily for 5 days). During these days, the mice showed a decrease in locomotor activity and exhibited akinesia in both pole and traction tests. Light microscopically, 44% of the MPTP-treated mice showed neuronal degeneration in the substantia nigra 1 month after the withdrawal (damaged group), and 56% showed no change (undamaged group). Morphometric analysis revealed that the number of neurons in the substantia nigra decreased by 33% on the average in both groups. Electron microscopically, an electron-dense degeneration of most neurons was seen in the substantia nigra of the damaged group, and even in the undamaged group, loss of rough endoplasmic reticulum and mitochondrial deformity were seen in 50-70% of the neurons. Electron-dense bodies were seen in the striatum of both groups. These results show the validity of the MPTP-treated C57 BL mice as a suitable model for parkinsonism, including Parkinson's disease.
 ...
PMID:Evaluation of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mouse model for parkinsonism. 235 77

Idiopathic Parkinson's Disease arises from the progressive loss of dopamine (DA)-utilizing neurons of the nigrostriatum and responds to the replacement of DA with L-dihydroxyphenylalanine (L-DOPA). In awake rats, with unilateral lesions induced with 6-hydroxydopamine (6-OHDA) of the DA-utilizing nigrostriatal pathway, treatment with L-DOPA causes the rapid onset of brisk contralateral turning behaviour. In urethane-anesthetized rats with identical unilateral lesions of the nigrostriatum, dialysis of the striatum, performed before and after the systemic administration of L-DOPA (25 mg/kg i.p.), did not demonstrate any alteration in extracellular DA in the striatum which was DA-deprived compared to intact striata. After treatment with L-DOPA extracellular levels of the metabolites of DA. DOPAC and HVA increased several fold. These results suggest: (a) DA neurons surviving after extensive lesions with 6-OHDA can compensate for loss of DA in the striatum and maintain extracellular fluid (and presumably synaptic) concentrations of DA; (b) in striata with extensive depletion of DA L-DOPA undergoes rapid decarboxylation to DA, followed by catabolism to DOPAC and HVA; and (c) in urethane-anesthetized animals, DA formed from DOPA does not appear to enter a releasable pool.
 ...
PMID:The metabolism of systemically-administered L-dihydroxyphenylalanine, by intact and dopamine-denervated striata, as revealed by brain microdialysis. 259 66

Methylated beta-carboline compounds are mammalian indole metabolites that we have proposed to be endogenous neurotoxins due to their structural similarity to MPP+, the active oxidized product of the dopaminergic toxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Several laboratories have demonstrated that MPP+ administration into the substantia nigra or median forebrain bundle of rats results in extensive depletion of striatal dopamine and its metabolites. We now report that three weeks after intranigral injection of the beta-carboline, 2-methyl-norharman, striatal dopamine, DOPAC, and homovanillic acid (HVA) concentrations ipsilateral to the injection are reduced 41-64% compared to vehicle-injected controls; in individual animals dopamine depletions of 96% were achieved. In addition, at the 2-methyl-norharman injection site in the substantia nigra, large lesions and gliosis were apparent under light microscopic examination. This is the first direct demonstration that a 2-methyl-beta-carbolinium ion is neurotoxic. It lends further validity to the hypothesis that MPP+-like beta-carbolines may be endogenous causative agents in Parkinson's disease.
 ...
PMID:Striatal dopaminergic toxicity following intranigral injection in rats of 2-methyl-norharman, a beta-carbolinium analog of N-methyl-4-phenylpyridinium ion (MPP+). 259 20

Systemic exposure to the neurotoxin MPTP produces a Parkinsonian syndrome in man and primates, but not in adult rats. However, embryonic rat dopamine neurons in cell cultures are selectively destroyed by MPTP. This study examined whether similar effects on dopamine neurons occur in vivo, by studying dopamine-mediated behaviors in rats prenatally treated with MPTP or its active metabolite MPP+. Pregnant rats were injected daily with MPTP, MPP+, or vehicle from gestational day (E)13 until birth. There were time-dependent increases in spontaneous locomotor and rearing activity. Offspring of both the MPTP and MPP+ groups were hyporesponsive to d-amphetamine (1 mg/kg IP) at postnatal day 21. This hyporesponsiveness persisted at postnatal day 50 in the pups from MPTP-treated mothers. However, the striatal concentration of dopamine and its metabolites DOPAC and HVA were not significantly affected by the prenatal MPTP or MPP+ treatments. Both MPTP and MPP+ groups had significantly increased stereotypic responses to apomorphine (0.2 mg/kg SC) on both postnatal days 21 and 50. These results demonstrated persistent postsynaptic supersensitivity to dopaminergic agonists following prenatal MPTP/MPP+ treatment. That fetal rats develop long-term sequelae after prenatal exposure to MPTP/MPP+ suggests a different sensitivity of the immature rat dopamine neurons than in adult rats. Understanding this difference may provide useful information in the development of animal models of Parkinson's Disease.
 ...
PMID:The effect of prenatal treatment with MPTP or MPP+ on the development of dopamine-mediated behaviors in rats. 262 12


1 2 3 4 5 6 7 8 9 10 Next >>