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)

A systematic study of the central and peripheral nervous systems in 3 cases of Parkinson's disease has demonstrated that Lewy bodies are present in 27 nuclei. Of these 20 nuclei (12 pigmented and 8 unpigmented) are involved in 2 or all 3 cases. It is noticed that the distribution of Lewy bodies in Parkinson's disease described here corresponds surprisingly well to that of monoamine (dopamine, noradrenaline and serotonin) cell bodies demonstrated in rats by the histochemical fluorescence method. This correlation is similar to that of Alzheimer's neurofibillary changes in postencephalitic Parkinsonism as described by Ishii. Inasmuch as these viewpoints are also in agreement with preciously reported biochemical data on Parkinsonism, it is suggested that Parkinsonism (idiopathic and postencephalitic) should represent a system degeneration of monoamine neuron systems.
 ...
PMID:Parkinson's disease: distribution of Lewy bodies and monoamine neuron system. 17 63

L-DOPA-psychosis is a frequent side effect of the combined treatment of Parkinson's disease with L-DOPA and peripherally active decarboxylase inhibitors. Regional human post-mortem brain studies showed a significant increase of noradrenaline and serotonin particularly in extrastriatal areas, whereas the lenticular nuclei were not involved. The significance of extrastriatal neurotransmitter dysfunctions for psychiatric disorders is discussed.
 ...
PMID:Toxic delirium after L-dopa medication. 29 Jul 36

The naturally occurring catecholamines, noradrenaline, adrenaline and dopamine, have been found in a wide range of animal and vegetable tissues, but are particularly associated with nervous tissue in animals. Of the many processes affecting the response to stimulation of catecholamine containing nerves, the synthesis of catecholamines, particularly the first enzymatic stage involving tyrosine hydroxylase, and the re-uptake process, whereby the nerve recovers much of the released catecholamine, appear to be the most significant. In peripheral tissues noradrenaline appears to be involved predominantly in the sympathetic control of blood pressure and flow while adrenaline is more important to metabolic processes especially fat and glucose turnover. Both may be released in increased amounts by various stimuli that cause stress or arousal in the body. Dopamine has not yet been shown to have any significant physiological function in peripheral tissues. In the central nervous system, noradrenaline and dopamine are the two main catecholamines. The working of the brain is complex and involves balanced interactions between a variety of neurotransmitters, known or as yet unrecognised. However, noradrenaline appears to play a role in the central control of blood pressure, and in determining mood and activity probably by affecting the emotional drives. Dopamine is certainly important in the control of motor pathways, as shown by the dopamine deficiency syndrome in Parkinson's disease, and is possibly of significance in the abnormal behaviour of psychotics. The role of the small concentration of adrenaline in the brain has yet to be fully established.
 ...
PMID:Catecholamines: role in health and disease. 36

Studies of pulse rate and blood pressure responses to graded intravenous infusions of noradrenaline and dopamine were performed on five patients with Parkinson's disease, five with the Shy-Drager syndrome and seven healthy subject. Cardiovascular reflex responses to standing and to the Valsalva manoeuvre were found to be preserved in all patients with Parkinson's disease but to be grossly defective or absent in all with the Shy-Drager syndrome. Each subject received separate intravenous infusions of L-noradrenaline and dopamine, delivered at increasing rates, until a 30% rise in systolic blood pressure was achieved. Heart rate decreased during pressor responses to noradrenaline in control subjects and patients with Parkinson's disease, but increased in those with the Shy-Drager syndrome. Heart rate increased during pressor responses to dopamine in all subjects. Compared to control subjects supersensitivity to noradrenaline was observed both in patients with Parkinson's disease and, to a greater extent, in those with the Shy-Drager syndrome. Subsensitivity to dopamine was observed in patients with Parkinson's disease, but supersensitivity in those with the Shy-Drager syndrome.
 ...
PMID:Blood pressure responses to noradrenaline and dopamine infusions in Parkinson's disease and the Shy-Drager syndrome. 78 43

1. Significantly reduced values of noradrenaline in Parkinson's disease were observable in all brain areas which were studied. 2. A topographic distribution of free 3-methoxy-4-hydroxyphenylglycol (MHPG) can be demonstrated in the human brain. As MHPG in the various brain areas shows a different pattern of concentration it seems that this metabolite of noradrenaline is of physiological significance and is able to reflect noradrenaline turnover. The highest values of free MHPG were found in the hypothalamus, n. accumbens, thalamus and n. ruber. 3. In a limited series of patients with Parkinson's disease post mortem analysis indicated lower values of MHPG in caudate n., putamen, s. nigra, red nucleus and n. accumbens. All other brain areas did not show significant alterations. 4. Parkinsonian patients who died during Madopar therapy demonstrated a significant increase of MHPG in caudate n., putamen, s. nigra, n. ruber, n. amygdalae and n. accumbens when compared to the untreated group, indicating an enhanced turnover of noradrenaline in these areas. 5. Bound MHPG has been estimated in various brain areas as to be in the range of 13--38 percent of free MHPG.
 ...
PMID:Brain-noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's syndrome. 92 85

1 The sensitivity of single neurones to microelectrophoretically applied dopamine, noradrenaline (NA), 5-hydroxytryptamine (5-HT) and acetylcholing (ACh) was investigated in the caudate nucleus of the rat, anaesthetized with halothane. Both excitatory and depressant responses could be observed to each of the agonists. There was a high correlation between the direction of responses to dopamine and noradrenaline, whereas there was no significant correlation between the direction of responses to dopamine and ACh. 2 The effect of desipramine was studied on both excitatory and depressant responses to dopamine, NA and 5-HT, and on excitatory responses to ACh. Both potentiation and antagonism of neuronal responses to monoamines and ACh could be observed after a brief application of desipramine. 3 Excitatory responses to glutamate were not affected by desipramine. 4 The observation that responses to dopamine and NA can be potentiated by desipramine in the caudate nucleus suggests that uptake blockade is not a prerequisite for potentiation. 5 It is suggested that the potentiation of neuronal responses to dopamine by desipramine may be responsible for the therapeutic efficacy of desipramine in Parkinson's disease.
 ...
PMID:Effects of desipramine on neuronal responses to dopamine, noradrenaline, 5-hydroxytryptamine and acetylcholine in the caudate nucleus of the rat. 116 88

The results of kinetic analysis of synaptosomal uptake of dopamine, noradrenaline, adrenaline and serotonin showed the presence of their own carrier systems with high or low affinity for each monoamine. The low affinity system of the uptake of monoamines by nerve endings differs from extraneuronal one by higher affinity. MPTP noncompetitively inhibits the system of highly effective uptake of the studied monoamines by nerve endings, competitively inhibiting synaptosomal uptake with low affinity of noradrenaline, adrenaline and noncompetitively serotonin and dopamine. The constant values of inhibition showed that MPTP most strongly blocks the system of synaptosomal uptake of low affinity serotonin and approximately 2-times weaker affects its system of high affinity. Carrier systems of high affinity of dopamine, adrenaline and noradrenaline block MPTP 150-500 times weaker than that of serotonin, and as for low affinity--in 2000-4000 times. It may be supposed that synaptosomal uptake of low affinity serotonin is most perceptible to the effect of MPTP and is of a particular importance in the development of Parkinson's disease symptoms.
 ...
PMID:[The effect of MPTP on the neuronal uptake of monoamines]. 129 Aug 21

We report an autopsied case of Parkinson's disease manifesting Shy-Drager syndrome. At the age of 63 years, the patient noticed an onset of progressive orthostatic dizziness, which was followed by constipation, dysuria, and sexual impotence. When he was 66 years old, syncopal attack for a few minutes, tremor in the bilateral hands, and memory disturbance developed. On admission, his blood pressure was 142/72 mmHg in supine position, which fell to 58/42 mmHg on standing with appropriate increase of heart rate. Neurological examination revealed hallucination, memory disturbance, masked face, muscular rigidity, bradykinesia, mild postural tremor, and autonomic dysfunction including severe orthostatic hypotension, hypohydrosis, constipation, dysuria, and sexual impotence. Electroencephalogram showed diffuse slowing. Brain CT demonstrated absence of severe atrophy of the cerebellum, and brain stem. Pharmacological study revealed denervation hypersensitivity to the intravenously administrated noradrenaline. A diagnosis of Shy-Drager syndrome was made, and he was treated with anti parkinsonian drugs. However, no improvement was observed in his clinical symptoms. Seven months later, he died of pneumonia. Neuropathological examination revealed marked neuronal cell loss and gliosis in the substantia nigra and locus ceruleus. Lewy bodies were seen in those pigmented nuclei, dorsal vagal nucleus, hypothalamus and nucleus basalis of Meynert. No abnormality was found in the intermediolateral nucleus of the spinal cord. This is the first report on a Japanese patient who presented clinically Shy-Drager syndrome and pathologically typical Parkinson's disease. In this patient, from the pharmacological and pathological findings, sympathetic ganglia were supposed to be the responsible lesion for orthostatic hypotension.
 ...
PMID:[An autopsied case of Parkinson's disease manifesting Shy-Drager syndrome]. 130 25

Male retired breeder C57/Bl and CD-1 mice were treated with either MPTP or its vehicle. At 7-10 days post-treatment, catecholamine concentrations within the olfactory bulbs (OB) and hypothalamus were determined. Norepinephrine concentrations within the OB were significantly decreased in MPTP-treated mice. These effects were more pronounced in the CD-1 (50% reduction) compared to the C57/Bl (20% reduction) strain. No effects of MPTP were observed on norepinephrine concentrations within the hypothalamus. Dopamine concentrations in the OB and hypothalamus did not differ between MPTP- and vehicle-treated mice in either strain. Overall, catecholamine concentrations within the OB, but not the hypothalamus, were significantly greater in C57/Bl compared to CD-1 mice. The reduction in OB norepinephrine concentration in the MPTP-treated animals may be related to the olfactory deficits which accompany Parkinson's disease.
 ...
PMID:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces norepinephrine concentrations in the olfactory bulbs of male mice. 151 43

Irreversible and unspecific inhibitors of MAO were the first modern antidepressants, but after an initial success they fell into discredit due to adverse side effects. In the past two decades interest in MAO inhibitors has been renewed because of progress in basic research, a milestone being the finding that there are two subtypes of MAO, MAO-A and MAO-B. These are distinct proteins with high amino acid homology, coded by separate genes both located on the short arm of the human chromosome X. The enzyme subforms show different substrate specificities in vitro and different distributions within the central nervous system and in peripheral organs. In the central nervous system of man MAO-A seems to be mainly involved in the metabolism of 5 HT and noradrenaline, whereas 2-phenylethylamine and probably dopamine are predominantly deaminated by MAO-B. In the intestinal tract tyramine is mainly metabolized by MAO-A. These characteristics indicate distinct physiological functions of the two MAO-subforms. Several irreversible and reversible non-hydrazine inhibitors with relative selectivities for one of the MAO-subforms have been developed. They belong to various chemical classes with different modes of enzyme inhibition. These range from covalent mechanism based interaction (e.g. by propargyl- and allylamine derivatives) to pseudosubstrate inhibition (e.g. by 2-aminoethyl-carboxamides) and non-covalent interaction (e.g. by brofaromine, toloxatone and possibly moclobemide). The most important pharmacological effects of the new types of MAO inhibitors are those observed in neuropsychiatric disorders. The inhibitors of MAO-A show a favorable action in various forms of mental depression. The drugs seem to have about the same activity as other types of antidepressants, including tricyclic and related compounds as well as classical MAO inhibitors. The onset of action of the MAO-A inhibitors is claimed to be relatively fast. Other possible indications of these drugs include disorders with cognitive impairment, e.g. dementia of the Alzheimer type. In subjects with Parkinson's disease the MAO-B inhibitor L-deprenyl exerts a L-dopa-sparing effect, prolongs L-dopa action and seems to have a favorable influence regarding on-off disabilities. The action is in general transitory (months to several years). In addition L-deprenyl has been shown to delay the necessity for L-dopa treatment in patients with early parkinsonism. Whether the drug influence the progression of the disease is still a matter of debate. L-deprenyl also appears to have some antidepressant effect (especially in higher doses) and to exert a beneficial influence in other disorders, e.g. dementia of the Alzheimer type.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The new generation of monoamine oxidase inhibitors. 160 14


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