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)

Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.
 ...
PMID:Uptake and efflux of 14-C-dopamine in platelets: evidence for a generalized defect in Parkinson's disease. 23 81

Dopamine and its specific receptors are widely distributed in man. Body regions where dopaminergic activity is of special pharmacologic interest include the basal ganglions, hypothalamus, chemoreceptor trigger zone, other less well defined areas in the central nervous system, and the renal and cardiovascular systems. The search for dopaminergic agents to modify these systems in disease states has depended heavily on in vitro and in vivo bioassays. These assays involving receptor binding, enzyme activation, smooth muscle and neuronal excitation, and modification of animal behavior have provided physicians with important therapeutic tools. Indeed, the introduction of levodopa for the treatment of Parkinson's disease and of the phenothiazines and related drugs for schizophrenia and psychosis has been a hallmark of neuropharmacologic research. However, the maximal benefits that these drugs may afford have not yet been realized due to an inadequate understanding of disease processes and a relative lack of specificity of drug action.
 ...
PMID:Clinical aspects of dopamine agonists and antagonists. 35 76

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

Dopamine (DA) sensitive adenylate cyclase activity was measured in homogenates of caudate nucleus and putamen from frozen brain of eight Parkinsonian patients and nine controls. In the control group, there was no difference in enzyme activity in respect to sex or age (21--77 years old). Caudate nucleus and putamen exhibited similar mean activity. In the Parkinsonian group, there was a significant decrease in both basal (by 50%) and DA stimulated (by 80%) activities compared with that of control group. This suggests that there may exist a functional disturbance in the postsynaptic (post-DA-nergic) region in the striatum of patients with Parkinson's disease; in addition, the decrease in basal as well as DA stimulated activity as measured in homogenates may not be the biochemical substrate for the hypothetical "denervation supersensitivity" expected to occur in Parkinson's disease.
 ...
PMID:Dopamine-sensitive adenylate cyclase activity in the striatum in Parkinson's disease. 45 31

Dopamine-Beta-Hydroxylase (D.B.H.)-activity was measured in the plasma of untreated Parkinsonian patients, after tretment with L-dopa and 2-Bromo-alpha-ergocriptine. The findings were compared to the D.B.H.-activity of a matched healthy control group. After L-dopa loading D.B.H.-activity decreased in the Parkinsonian patients by 27.6 +/- 3.1% compared to 16.2 +/- 3.3% (p less than 0.02) in the control group. After 2-Bromo-alpha-ergocriptine laoding the decrease in D.B.H.-activity was 32.6 +/- 4.4% in the parkinsonian patients, and 158 +/- 4.9% (p less than 0.02) in the control group. This reduced D.H.B.-activity after L-dopa loading may reflect an impairment, in the Parkinsonian patients' ability to metaoblize L-dopa. The reduced D.B.H.-activity after treatment with 2-Bromo-alpha-ergocriptine may be explained by a pronounced antagonistic influence of 2-Bromo-alpha-ergocriptine on the presynaptic dopamine receptors, suggesting that presynaptic dopaminergic receptors are involved in Parkinson's disease.
 ...
PMID:Plasma dopamine beta hydroxylase (D.B.H.) activity in Parkinsonian patients under L-dopa, and 2-bromo-alpha-ergocriptine loading. 50 50

Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practical in vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkisonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor. A new form of therapy, based on this concept, is proposed.
 ...
PMID:Molecular biology of neurological and psychiatric disorders. I. Effect of parkinsonism, age, sex and L-dopa on platelet monoamine oxidase. 97 97

Dopamine-containing neurons of the mammalian midbrain are required for normal behavior and movements. In vivo they fire action potentials in bursts, but in vitro they discharge regularly spaced action potentials. Burst firing in vitro has now been shown to be robustly induced by the glutamate agonist N-methyl-D-aspartate (NMDA) although not by the non-NMDA agonists kainate or quisqualate. The hyperpolarization between bursts of action potentials results from electrogenic sodium ion extrusion by a ouabain-sensitive pump. This mechanism of burst generation in mammalian neurons may be important in the pathophysiology of schizophrenia and Parkinson's disease.
 ...
PMID:Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump. 132 9

Treatment of Parkinson's disease (PD) can be divided into two categories: symptomatic therapy (restoring dopamine levels toward normal and reversing functional disability) and preventive therapy (interfering with the pathophysiologic mechanism of PD to prevent or decrease the rate of progression of the disease). Regarding symptomatic treatment, although anticholinergic preparations generally are considered effective for the symptoms of tremor and rigidity without altering bradykinesia, their effectiveness is limited and adverse reactions are common; their role should be restricted to use as adjuvants to levodopa therapy. Amantadine has been shown to be as effective as anticholinergics, but it lacks long-term efficacy. Dopamine agonists--bromocriptine, pergolide mesylate and lisuride in Europe--are not as effective as levodopa and therefore rarely are used as initial therapy; their proposed role, too, is as adjuvants to levodopa therapy. Levodopa is the most effective drug presently available for the treatment of PD; its introduction is accompanied by rapid and dramatic reduction of symptoms and signs. Initial adverse reactions are not usually a major problem; and although there is speculation that initiation of therapy should be delayed because of possible long-term complications, clinically distinguishing these from problems related to disease progression itself is difficult. The possibility that nigral cell death is mediated by oxidative mechanisms provides the basis for considering antioxidant therapy as protective treatment; selegiline, an antioxidant, has been found to delay the need for symptomatic therapy. It is suggested that initial treatment of Parkinson's disease begin with both preventive therapy with selegiline and symptomatic treatment with the sustained-release preparation of levodopa, which may be associated with fewer long-term complications.
 ...
PMID:Initiating treatment of Parkinson's disease. 134 9

Dopamine-stimulated adenylyl cyclase activity was measured in striatal homogenates of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys and humans with idiopathic Parkinson's disease and compared with the activity in control tissue. No differences between parkinsonian and control tissue were found in the presence of 20 mM NaCl. However, when 120 mM NaCl was included in the assay medium, a significantly higher increase in the Vmax of dopamine-stimulated adenylyl cyclase activity was observed in the caudate of MPTP-parkinsonian rhesus monkeys and the putamen of patients with idiopathic Parkinson's disease. No such sensitization was seen in the MPTP-treated rhesus putamen or human Parkinson's disease caudate tissue. A role of D2 receptors in this sensitization could be ruled out by the concomitant use of the D2 antagonist l-sulpiride and by [3H]spiperone saturation analysis of the D2 receptor density, which was found at control level in the caudate tissue of MPTP-treated rhesus monkeys. Similarly, on the basis of saturation binding with the D1 selective ligand 125I-SCH 23982, there was no difference in caudate nucleus D1 receptor densities between control and MPTP-treated monkeys. Our results point to a region-specific functional sensitization of D1 receptors as a consequence of severe dopaminergic denervation of the striatum and suggest the possibility of a therapeutic potential of a D1 agonist with full intrinsic activity in Parkinson's disease.
 ...
PMID:Sensitization of dopamine-stimulated adenylyl cyclase in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys and patients with idiopathic Parkinson's disease. 134 41

Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.
 ...
PMID:Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification. 135 58


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