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)

1. NPY is a 36 amino acid tyrosine-rich peptide. It is one of the most abundant and widely distributed neuropeptides known today within the central nervous system with particularly high concentrations in the hypothalamus and in several limbic regions. 2. NPY seems to coexist with other on neurotransmitters like somatostatin, galanin, GABA and the catecholamines noradrenaline and adrenaline in discrete brain regions. 3. NPY binding sites are widely distributed in the brain. However they do not always overlap with the distribution of NPY-like immunoreactivity. 4. NPY is suggested to be involved in a large number of neuroendocrine functions, stress responses, circadian rhythms, central autonomic functions, eating and drinking behaviour, and sexual and motor behaviour. 5. Psychotropic drugs and neurotoxins can alter the NPY concentrations in discrete brain regions. 6. It is possible that NPY is related to various neurological and psychiatric illnesses, like Huntington's chorea, Alzheimer's disease, Parkinson's disease, eating disorders, and major depressive illness.
 ...
PMID:Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorders. 266 85

The capacity of the spinal cord of the rat to synthesize and metabolize catecholamines from injected L-DOPA, was tested at 10 and 100 days after a middle thoracic transection of the cord. There was no indication of even a minimal recovery of the capacity to synthesize noradrenaline in the caudal region of the transected cord. At 10 days after transection, the lumbar cord could synthesize 50% of the dopamine formed in the intact cord. At 100 days after transection the synthesis of dopamine in the transected cord was equal to that in the intact control animal. At both 10 and 100 days after transection, the dopamine synthesized from L-DOPA was efficiently metabolized to dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). As judged from the levels of gamma-aminobutyric acid (GABA) and glutamic acid (glutamate) present in the transected cord, no major metabolic derangement of the spinal cord tissue seemed to have been present at the times the experiments were done. It is concluded that dopamine can be efficiently synthesized and metabolized from its immediate precursor, L-DOPA, even in the absence of monoaminergic nerves. The results are discussed with reference to two main themes. The first, is the likelihood that in the therapeutic use of L-DOPA in states of chronic dopaminergic nerve degeneration (e.g. Parkinson's disease), the synthesis and metabolism of dopamine probably occurs throughout the entire central nervous system. The second, is the possible usefulness of L-DOPA to test for the relative intactness of spinal reflex circuities in the chronically spinalized animal.
 ...
PMID:The synthesis and metabolism of catecholamines in the spinal cord of the rat after acute and chronic transections. 286 84

The evidence for deficiencies in neurotransmitters in Alzheimer's disease is reviewed. Major losses occur in the subcortical afferent projection systems based on acetylcholine, noradrenaline and serotonin. Within the cortex, somatostatin containing neurones and the large pyramidal cells, presumed to use glutamate/aspartate as transmitters, are the most severely damaged cells. The anatomical distribution of cell loss is explainable if the primary site of damage lies within the cortex; nerve cells are damaged by virtue of their presence within or their connections to this region. The senile plaque may represent the site of this damage and neurofibrillary tangle formation and accumulation may lead to cell death. In patients with Down's syndrome who live past 40 years, changes in transmitters apparently identical to those in Alzheimer's disease occur. The dementia of Parkinson's disease appears related to damage to cholinergic, noradrenergic and dopaminergic systems and may reflect a failure of these subcortical regions to sufficiently "activate" an otherwise undamaged cortex.
 ...
PMID:Neurotransmitter deficits in Alzheimer's disease and in other dementing disorders. 287 73

The neuroendocrine function is regulated by several neurotransmitters (acetylcholine, dopamine, somatostatin and noradrenaline) known to be reduced in brains of patients with Alzheimer's disease (AD). Moreover, the hypothalamus also has pathological changes. In spite of these findings suggesting neuroendocrine dysfunctions, this function has seldom been investigated in AD patients so far. We have compared patients with clinically 'probable' AD of mild-to-moderate severity with nondemented age- and sex-matched controls. Plasma levels of prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH) were measured by commercially available radioimmunoassays (RIA) before and after stimulation with metoclopramide, l-dopa or thyrotropin-releasing hormone. Basal plasma levels of beta-endorphin and beta-lipotropin were measured by RIA after high-performances liquid chromatography. Basal and stimulated plasma levels of PRL, GH, TSH and beta-lipotropin were similar in the two groups. Basal lamina levels of beta-endorphin were significantly higher in the patient group. Of doubtful clinical importance, this might be attributed to decreased tuberoinfundibular dopaminergic activity and has also been seen in patients with Parkinson's disease.
 ...
PMID:Neuroendocrinological function in Alzheimer's disease. 297 29

From the data discussed in this review it appears that GABA receptor agonists exhibit a variety of actions in the central nervous system, some of which are therapeutically useful (Table V). GABA receptor agonists, by changing the firing rate of the corresponding neurons accelerate noradrenaline turnover without changes in postsynaptic receptor density and diminish serotonin liberation with an up-regulation of 5HT2 receptors. These effects differ from those of tricyclic antidepressants which primarily block monoamine re-uptake and cause down-regulation of beta-adrenergic and 5HT2 receptors. The GABA receptor agonist progabide has been shown to exert an antidepressant action which is indistinguishable from that of imipramine in patients with major affective disorders. The fact that: (a) GABA receptor agonists and tricyclic antidepressants affect noradrenergic and serotonergic transmission differently; and (b) tricyclic antidepressants alter GABA-related parameters challenges the classical monoamine hypothesis of depression and suggests that GABA-mediated mechanisms play a role in mood disorders. Decreases in cellular excitability produced by GABAergic stimulation leads to control of seizures in practically all animal models of epilepsy. GABA receptor agonists have a wide spectrum as they antagonize not only seizures which are dependent on decreased GABA synaptic activity but also convulsant states which are apparently independent of alterations in GABA-mediated events. These results in animals are confirmed in a wide range of human epileptic syndromes. GABA receptor agonists decrease dopamine turnover in the basal ganglia and antagonize neuroleptic-induced increase in dopamine release. On repeated treatment, progabide prevents or reverses the neuroleptic-induced up-regulation of dopamine receptors in the rat striatum and antagonizes the concomitant supersensitivity to dopaminomimetics. Behaviorally, GABA receptor agonists diminish the stereotypies induced by apomorphine or L-DOPA suggesting that GABAergic stimulation results also in an antidopaminergic action which is exerted beyond the dopamine synapse. These effects of GABA receptor agonists may represent the basis of the antidyskinetic action of these compounds which, however, remains to be fully confirmed. GABA receptor agonists reduce striatal acetylcholine turnover, an effect which occurs at doses much lower than those which affect dopamine neurons. Since hyperactivity of cholinergic neurons plays a determinant role in the pathogenesis of some parkinsonian symptoms, it is conceivable that GABAergic stimulation is effective in ameliorating Parkinson's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:GABA receptor agonists: pharmacological spectrum and therapeutic actions. 298 90

The Parkinson-syndrome is the most important syndrome under the extrapyramidal disease. The therapy with L-DOPA has a prominent place in the therapy of Parkinson disease since the introduction of oral effective drugs. Dopamin has an effect to the basalganglia as a neurotransmitter and perhaps an inhibition effect to specific synapses of brain. The inhibition or the optimal balance of the cholinergic systems is the effect of Dopamin and Noradrenalin. The therapy with low dosis of L-DOPA in combination with a decarboxylase-inhibitor will be prevent the side-effects of nerv-cells.
 ...
PMID:[Thoughts on the neurobiological aspects of Parkinson syndrome]. 301 Mar 57

L-Threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was administered as a means of treating akinesia in 9 patients with Parkinson's disease and one with pure akinesia. Akinetic symptoms were improved in 7 of 10 patients. During chronic L-threo-DOPS treatment, cerebrospinal fluid (CSF) and plasma concentrations of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and L-threo-DOPS were measured in these 10 patients. The results show that there were no significant changes in either CSF or plasma free MHPG concentrations before or during L-threo-DOPS administration. The L-threo-DOPS concentration during treatment was not measurable in the CSF of 2 patients nor in the plasma of 1 out of 4 patients given only L-threo-DOPS. It was, however, measured in all patients treated with a combination of L-threo-DOPS and L-DOPA plus carbidopa. The results show that L-threo-DOPS is transported into the CSF, and suggest that its active mechanism may be further clarified by studying its action on not only noradrenaline, but also other neurotransmitters.
 ...
PMID:Effect of L-threo-3,4-dihydroxyphenylserine chronic administration on cerebrospinal fluid and plasma free 3-methoxy-4-hydroxy-phenylglycol concentration in patients with Parkinson's disease. 308 14

(-)Deprenyl (Selegilinum hydrochloricum, Jumex, Eldepryl) developed in the early sixties as a new spectrum, potent, irreversible MAO blocker (Knoll et al., 1965) was introduced as the first selective inhibitor of B-type MAO (Knoll and Magyar, 1972). In striking contrast to MAO inhibitors which strongly potentiate the pressor effect of tyramine, (-)deprenyl was described to inhibit the tyramine-induced release of noradrenaline in vascular smooth muscle (Knoll et al., 1968). The peculiar pharmacological spectrum of (-)deprenyl allowed its use as an adjuvant to the levodopa therapy of Parkinson's disease (for review see Birkmayer and Riederer, 1985). Levodopa therapy revolutionized the medication of Parkinson's disease, but severe side-effects forced the search for adjuvants with a levodopa-sparing effect. Peripheral decarboxylase inhibitors are now efficiently used for this purpose. It was reasonable to expect further potentiation and prolongation of the effect of levodopa in parkinsonians with concurrent administration of MAO inhibitors. A number of irreversible inhibitors of this type were tested in combination with levodopa, and potentiation of the antiakinetic effect of the latter was demonstrated; however, the supervention of distressing side-effect (greatly increased involuntary movements, hypertensive reactions, toxic delirium) terminated any further work along this line. There was a concensus that to give MAO inhibitors concurrently with levodopa was contra-indicated. This conclusion was called in question, however, by the development of deprenyl. (-)Deprenyl is a safe MAO inhibitor which can be given concurrently with levodopa and a peripheral decarboxylase inhibitor for the long run without the supervention of any distressing side-effects. For details regarding the pharmacology of (-)deprenyl we refer a number of reviews (Knoll 1976, 1978, 1980, 1982, 1983, 1986). The aim of this paper is to give a brief survey of the most important experimental data which demonstrate that (-)deprenyl facilitates dopaminergic tone in the brain in a peculiar manner and gives a satisfactory explanation for the observation that long-term (-)deprenyl treatment prolongs the life span of parkinsonian patients significantly (Birkmayer et al., 1985).
 ...
PMID:The pharmacology of (-)deprenyl. 309 62

We investigated the effect of systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine (gamma-Glu-DOPA) on catecholamine contents in the brain. gamma-Glu-DOPA was transformed to dopamine (DA) in vitro with brain homogenate by the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase. Intraperitoneal injection of gamma-Glu-DOPA to mice increased DA markedly and noradrenaline (NA) moderately in the brain. The increase of endogenous DA was followed by elevation of the main DA metabolites (3,4-dihydroxyphenyl-acetic acid and homovanillic acid). These increases were in a dose-dependent manner. The maximal elevation of DA was observed within 30 min after administration of gamma-Glu-DOPA, but a substantial increase of NA was observed 2 h after the administration. These results suggest that gamma-Glu-DOPA may be applicable to the treatment of Parkinson's disease.
 ...
PMID:Increase of catecholamines in mouse brain by systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine. 311 8

One important function of the catecholamine innervation of the cerebral cortex may be the control of attention. Of particular interest are the catecholamine projections to the cerebral cortex from the reticular formation, namely the dopamine neurons of the ventral tegmentum of the midbrain and the noradrenergic neurons of the locus coeruleus in the upper pons. Animal studies implicate noradrenaline and dopamine in a wide range of attention-related behaviours involving search and exploratory activity, distractibility, response rate, discriminability and the switching of attention. Most human studies come from the clinical literature relating to schizophrenia, Parkinson's disease and attention deficit disorder. An association has been claimed in each of these conditions between abnormal catecholamine activity (in particular dopamine) and attentional dysfunction. In particular, difficulty with the attachment of appropriate responses to environmental stimuli, akin to those observed in animals with lesions to central dopamine pathways, indicates a role for dopamine in response selection processes. Overall, the animal and human studies reviewed indicate a role for central noradrenaline and dopamine in the early and late processing of information, respectively.
 ...
PMID:Catecholamines and attention. I: Animal and clinical studies. 332 64


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