Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-Evans dams were fed either a vitamin B6-deficient or a control diet from day 13-14 of gestation and throughout lactation. A control pair-fed group was also included because of differences in food intake between vitamin B6-deficient and control ad libitum dams. The progeny of vitamin B6-deficient dams had all the classic symptoms of B6 deficiency. These included weight loss, ataxia, tremor, and epileptic seizures. Concentrations of the neurotransmitter dopamine (DA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as D-2 dopamine receptor binding, 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activity, and vitamin B6 levels were measured in the corpus striatum of progeny at 7, 14, and 18 days after birth. Striatal DA and HVA levels were significantly decreased in B6-deficient animals when compared to ad libitum or pair-fed controls. Daily injections of vitamin B6 to deprived animals from the 14th to 18th day after birth improved the abnormal movement and normalized the concentration of DA but not of HVA in corpus striatum. Striatal D-2 dopamine receptor binding using [3H]spiperone as ligand was significantly reduced in 18-day-old animals as compared to ad libitum and pair-fed controls. No significant differences were found at 14 days. The administration of vitamin B6 to deprived animals did not raise the level of D-2 receptor binding during the period of observation. Scatchard plots indicated that the differences in binding were due to changes in receptor number and not in KD. Corpus striatum DOPA decarboxylase activity with and without the addition of exogenous pyridoxal phosphate was significantly reduced in 14- and 18-day-old animals when compared to pair-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of perinatal vitamin B6 deficiency on dopaminergic neurochemistry. 379 15

The effects of centrally acting drugs on tremor were investigated in monkeys with ventromedial tegmental lesions exhibiting hypokinesia or hypokinesia and tremor. In monkeys with resting tremor, the administration of DL-5-HTP (5-hydroxytryptophan) or of DL-DOPA (3,4-dihydroxyphenylalanine) relieves the tremor, but the simultaneous administration of DL-5-HTP or DL-DOPA and atropine results in a much more pronounced relief. These results point to an imbalance between the cholinergic and adrenergic-serotonergic systems in parkinsonism. In monkeys exhibiting hypokinesia, the administration of harmaline evokes a marked resting tremor of the extremities contralateral to the tegmental lesion. The production of tremor by harmaline is not abolished by lowering the striatal amine levels with specific inhibitors of amine synthesis. Administration of DL-5-HTP protects monkeys from tremors induced by harmaline, which might affect the functions of the central nervous system by interaction with receptors for serotonin. The present results further demonstrate the apparent role of biogenic amines in the extrapyramidal dysfunctions.
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PMID:The effects of centrally acting drugs on tremor in monkeys with mesencephalic lesions. 498 45

Isozymes of tobacco pith polyphenoloxidases (o-diphenol oxidase, EC 1.10.3.1) were separated electrophoretically from fresh pith of intact plants and from cultured pith sections. Extracts of fresh pith contained a poorly resolved complex of two to three anodic bands after starch gel electrophoresis at alkaline pH. This anodic complex was more active with chlorogenic acid than with 3,4-dihydroxyphenylalanine and was found in greater activity per gram fresh weight of tissue in younger internodes than in older ones. The longitudinal gradient of activity was thus the opposite of that found for the constitutive isozymes of peroxidase.A well defined cathodic band of polyphenoloxidase activity appeared after culture of pith in modified White's medium with shaking. This band, which was more active with 3,4-dihydroxyphenylalanine than with chlorogenic acid, could be detected after 1 to 2 days of incubation. Its appearance was enhanced by the addition of 10 mum indoleacetic acid; kinetin (1 mum tended to prevent this indoleacetic acid effect). Such hormonal control is opposite to that previously reported for the rapidly appearing new isozymes of peroxidase. The pattern of the major isozymes associated with polyphenoloxidase activities differs from that of peroxidase.
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PMID:Ontogeny and hormonal control of polyphenoloxidase isozymes in tobacco pith. 499 42

Ten free monoamines and their metabolites in plasma and cerebrospinal fluid (CSF) were simultaneous measured in 6 levodopa-untreated (LU), 18 levodopa-treated (LT) and 37 levodopa-withdrawn (LW) Chinese patients with Parkinson's disease (PD) and 26 controls. We found that the levels of these substances in LW patients were not significantly different from those in LU patients. In LU- and LW-PD patients, CSF epinephrine (EPI) was higher (P < 0.05) than that of the controls. 3-methoxy-DOPA (3-OMDOPA) might not inhibit the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and dopamine metabolites in CSF. Levodopa treatment might change the dopaminergic and serotoninergic neuronal systems, but not the noradrenergic or adrenergic neuronal systems, in CNS of PD patients. Benserazide (a peripheral decarboxylase inhibitor) in Madopar might decrease the levels of serotonin (5-HT) and norepinephrine (NE), but not those of DOPA and homovanillic acid (HVA), in plasma. HVA, NE and EPI in plasma were not good indices for those in CSF. Otherwise, our results were consistent with some other studies by showing a significantly lower level (P < 0.01) of HVA in CSF of LU- and LW-PD patients than that of the controls, while no difference for NE, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindole acetic acid (5-HIAA) or 3-OMDOPA was noted. The severity of clinical disability was related to the deficiency of CSF HVA and DOPAC in LU- and LW-PD patients; however, there was no relationship between clinical symptoms of tremor, rigidity-bradykinesia, autonomic dysfunction, dementia, depression or levodopa-induced dyskinesia and CSF monoamines or their metabolites.
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PMID:Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease. 833 58

The anti-tremor activity of talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride, B-HT 920 CL2, Domin), a non-ergot dopamine D2 receptor agonist which possesses alpha 2-adrenoceptor agonistic and 5-HT3 receptor antagonistic properties, was examined in monkeys with a unilateral lesion in the ventromedial tegmentum. Talipexole dose dependently suppressed the tremor and had ED50 values of 34 micrograms/kg s.c. and 84 micrograms/kg p.o. The anti-tremor effect of talipexole occurred at much lower doses than that of an ergot dopamine receptor agonist, bromocriptine (2-bromo-alpha-ergocryptine mesilate, ED50; 2.5 mg/kg s.c.), and talipexole acted synergistically in combination with L-DOPA (3,4-dihydroxyphenylalanine). In ventromedial tegmentum-lesioned monkeys, anti-tremor doses of talipexole did not cause emetic behavior, but had sedative effects. Conversely, monkeys given bromocriptine exhibited oral movement, salivation and vomiting when anti-tremor effects were observed, but not marked sedative behavior at any of the doses investigated. During repeated administration of talipexole (a daily dose of 50 micrograms/kg s.c. for 21 days), the extent and duration of the anti-tremor effect did not change, but those of the sedative effect decreased gradually. The anti-tremor effect of talipexole was significantly suppressed by sulpiride, but not by SCH 23390 (7-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) or yohimbine, while the sedative effect was inhibited by sulpiride and yohimbine. The main metabolites of talipexole had no anti-tremor or sedative effects. These results indicate that talipexole exerts its anti-tremor activity via selective dopamine D2 receptor stimulation.
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PMID:Anti-tremor activity of talipexole produced by selective dopamine D2 receptor stimulation in cynomolgus monkeys with unilateral lesions in the ventromedial tegmentum. 904 91

Antagonism of adenosine A2A receptor function has been proposed as an effective therapy in the treatment of Parkinson's disease. Thus, the study of new adenosine receptor antagonists is of great importance for the potential use of these drugs in clinical practice. The present study evaluated effects of the new preferential adenosine A2A receptor antagonist 2-butyl-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-6-ylamine (ST1535) in unilaterally 6-hydroxydopamine lesioned rats. Acute ST1535 dose-dependently potentiated contralateral turning behaviour induced by a threshold dose of l-3,4-dihydroxyphenylalanine (L-DOPA) (3 mg/kg i.p.), a classical test for antiparkinson drug screening. Subchronic (18 days, twice a day) ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not induce sensitization to turning behaviour or abnormal involuntary movements during the course of treatment, indicating a low dyskinetic potential of the drug. Moreover, while subchronic administration of a fully effective dose of L-DOPA (6 mg/kg i.p.) significantly increased GABA synthesizing enzyme glutamic acid decardoxylase (GAD67), dynorphin and enkephalin mRNA levels in the lesioned striatum, subchronic ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not modify any of these markers, although it induced a similar number of contralateral rotations at the beginning of treatment. Finally, acute administration of ST1535 (20 mg/kg i.p.) proved capable of reducing jaw tremors in tacrine model of Parkinson's disease tremor. Results showed that ST1535, in association with a low dose of L-DOPA, displayed antiparkinsonian activity similar to that produced by a full dose of L-DOPA without exacerbating abnormal motor side effects. Moreover, in agreement to other well characterized adenosine A2A receptor antagonists, ST1535 features antitremorigenic effects.
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PMID:Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: acute and subchronic studies in rats. 1744 98

Gait and balance disorders unresponsive to dopaminergic drugs in Parkinson's disease (PD) are secondary to lesions located outside the dopaminergic system. However, available animal models of PD fail to display l-3,4-dihydroxyphenylalanine (DOPA)-responsive parkinsonism and drug-resistant gait and balance disorders, and this lack of appropriate model could account for the deficit of efficient treatments. Because the pedunculopontine nucleus (PPN) plays an important role in locomotion control, we conducted the present study to investigate the consequences of combined dopaminergic and PPN lesions in a same animal. We used macaques that received first 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication to render them parkinsonian and then local stereotaxic lesion of the PPN. Adding bilateral PPN lesions in MPTP-lesioned macaques induced dopamine-resistant gait and balance disorders but unexpectedly improved hypokinesia. Additional MPTP injections resulted in the association of a severe DOPA-responsive parkinsonism together with DOPA-unresponsive gait disorders. Histological examination assessed a severe dopaminergic degeneration and a significant loss of PPN cholinergic neurons. We observed similar results in aged monkeys intoxicated with MPTP: they developed severe DOPA-responsive hypokinesia and tremor together with unresponsive gait and balance disorders and displayed dopaminergic lesion and a weak but significant cholinergic PPN lesion. Our results highlight the complex role of the cholinergic PPN neurons in the pathophysiology of PD because its lesion induces a dual effect with an improvement of hypokinesia contrasting with a worsening of DOPA-unresponsive gait and balance disorders. Thus, we obtained a primate model of PD that could be useful to test symptomatic treatments for these heavily disabling symptoms.
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PMID:Gait disorders in parkinsonian monkeys with pedunculopontine nucleus lesions: a tale of two systems. 2386 85

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra, the depletion of striatal dopamine and the presence of Lewy aggregates containing alpha-synuclein. Clinically, there are motor impairments involving cardinal movement symptoms, bradykinesia, resting tremor, muscle rigidity, and postural abnormalities, along with non-motor symptoms such as sleep, behavior and mood disorders. The current treatment for PD focuses on restoring dopaminergic neurotransmission by l-3,4-dihydroxyphenylalanine (levodopa), which loses therapeutic efficacy and induces disabling abnormal involuntary movements known as levodopa-induced dyskinesia (LID) after several years. Evidence indicates that the pathophysiology of both PD and LID disorders is also associated with the dysfunctional activity of the serotonergic (5-HT) neurons that may be responsible for motor and non-motor disturbances. The main population of 5-HT neurons is located in the dorsal raphe nuclei (DRN), which provides extensive innervation to almost the entire neuroaxis and controls multiple functions in the brain. The degeneration of DRN 5-HT neurons occurs in early PD. These neurons can also take exogenous levodopa to transform it into dopamine, which may disturb neuron activity. This review will provide an overview of the underlying mechanisms responsible for 5-HT dysfunction and its clinical relevance in PD and dyskinesia.
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PMID:Dysfunction of serotonergic neurons in Parkinson's disease and dyskinesia. 3134 30