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)

1. Levodopa, dopamine, noraderanaline and adrenaline (in increasing order of potency) depressed the tension and degree of fusion of incomplete tetanic contractions of the slow-contracting soleus muscle in chloralose-anaesthetized cats. 2. The effects of all compounds were antagonized by propranolol (50-20 microgram/kg), but not practolol (1.0-5.0 mg/kg). This indicates that effects are mediated by beta2-adrenoceptor stimulation. 3. The effect of levodopa, but not of the catecholamines, was antagonized by prior administration of the dopa decarboxylase inhibitior benserazide. This indicates that levodopa itself is inactive, whereas its decarbodylated metabolites are active. 4. The depressant action of beta-adrenoceptor agonists on incomplete tetanic contractions of the cat soleus muscle, which are exerted directly on the muscle fibres, is a model for effects exerted on slow-contracting units of human muscles; the latter effects probably underlie the tremor observed after beta-adrenoceptor agonist administration. 5. These results therefore suggest that levodopa, via its decarboxylated metabolites, dopamine, noradrenaline and adrenaline, may produce or exacerabate tremor in man. Thus in Parkinsonian patients any centrally induced relief of tremor that levodopa may produce may be masked by tremorogenic effects of such metabolites exerted in the periphery.
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PMID:Peripheral muscle effects of levodopa in the anesthetized cat. 69 76

1. Tetrahydropapaveroline (THP) and isoprenaline have been compared for effects on heart rate, diastolic blood pressure and contractions of soleus and tibialis muscles in chloralose-anaesthetized cats and on in vitro guinea-pig soleus muscles. 2. All effects of THP were similar to those of isoprenaline. Maximal responses were the same and responses to both drugs were antagonized by propranolol. 3. THP produced an increase in heart rate, a fall in diastolic blood pressure and a decrease in the tension and degree of fusion of incomplete tetanic contractions of the soleus, being, respectively, 12.9, 14.7 and 19.6 times less potent than isoprenaline. The similarity in potency ratios suggests that THP is a non-selective beta-adrenoceptor agonist. 4. Effects on the guinea-pig soleus in vitro were similar to those in the cat soleus. 5. In the cat, THP enhanced the tension and duration of tibialis twitches, but the tibialis was about ten times less sensitive than the soleus to the effects of THP. 6. THP deepened neuromuscular blockade in partially curarized cat soleus and tibialis preparations. Doses required were ten times greater than for direct depressant effects on the soleus. 7. Agents which depress the tension and fusion of incomplete tetanic contractions of the cat soleus via beta-adrenoceptor stimulation cause tremor in man by peripheral effects on slow muscle fibres. THP is likely to exert such actions. This may explain why levodopa (a precursor of THP) sometimes precipitates a tremor crisis in Parkinsoniam patients, and why Parkinsonian tremor is relatively refractory to levodopa therapy. In such patients combination therapy with levodopa and a peripheral dopa decarboxylase inhibi;or (to reduce levels of THP) or a beta-adrenoceptor antagonist (to block the effects of THP on slow muscle fibres) could be advantageous.
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PMID:Actions of tetrahydropapaveroline on the cardiovascular system and skeletal muscles of the anaesthetized cat and on guinea-pig soleus muscle in vitro. 69 77

Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa.
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PMID:Treatment of parkinson's disease with bromocriptine. 98 85

A myoclonic syndrome consisting of tremor, myoclonus, and seizures was produced following the systemic administration of 5-hydroxytryptophan to adult rats previously given intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. This behavioral response was blocked by pretreatment with the putative serotonin receptor blocking agents methysergide, lysergic acid diethylamide, and bromolysergic and diethylamide, as well as centrally effective doses of the aromatic amino acid decarboxylase inhibitor Ro4-4602. Blockers of receptors of other neurotransmitters had little effect. This neurologic response in the adult rat may be relevant to some forms of clinical myoclonus and may be useful in testing potential agonists and antagonists of serotonin receptors in the mammalian central nervous system.
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PMID:Myoclonus after 5-hydroxytryptophan in rats with lesions of indoleamine neurons in the central nervous system. 108 96

Urinary excretion of DA, DOPAC, 3-MT, HVA, NMA, MA, VMA and 5-HIAA were studied in 33 parkinsonian patients treated with 1.5-7.5 g of levodopa daily for up to six months and in 30 patients receiving levodopa (800-1,000 mg) combined with a dopa decarboxylase inhibitor, benserazide (200-250 mg). Basal urinary excretions were within normal limits except for that of 3-MT which was significantly lower in parkinsonian patients as compared to controls. Levodopa induced an increase of about 400 fold in urinary DA; DOPAC was increased about 300 fold, 3-MT only about 70 fold, but HVA about 300 fold. Urinary NMA and MA did not change but VMA was increased significantly. On the other hand, urinary 5-HIAA was significantly decreased. The amounts of excreted DA and its subsequent metabolities were increased with the continuation of treatment, suggesting inductive phenomena in enzyme systems. During combined treatment with levodopa and benserazide urinary DA was increased, but only to about one tenth the extent seen with levodopa alone. The excretion of DOPAC was about one 20th, of 3-MT about one fourth and of HVA one 25th that seen during levodopa treatment. No signs of enzyme induction were seen. NMA was lowered significantly but MA remained unchanged. VMA was increased and significantly more than during therapy with levodopa alone. 5-HIAA was again significantly decreased and the decrease was significantly greater than that seen with levodopa alone. Some statistically significant correlations were seen between the excretions of NMA, MA and VMA and cardiovascular side effects, indicating an affection on the NA-ergic system by levodopa treatment. Significant correlation between 5-HIAA excretion and clinical improvement of tremor during levodopa treatment may suggest that participation of 5-HT in the mechanism of tremor.
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PMID:Urinary excretion of monoamines and their metabolites in patients with Parkinson's disease. Response to long-term treatment with levodopa alone or in combination with a dopa decarboxylase inhibitor and clinical correlations. 122 7

Levodopa (+ dopa decarboxylase inhibitor) is the most active of all drugs used in the treatment of Parkinson's disease. It acts on both akinesia and rigidity and improves the prognosis of the disease by increasing life expectancy. But levodopa also produces late side-effects: it often induces abnormal movements, fluctuations in motor performance, on-off effects, psychotic hallucinations, etc. Since these late side-effects remain difficult to treat, it is always necessary to assess the benefits and risks of the first treatment with levodopa. Anticholinergic drugs, which mainly act on tremor, must be used with caution since they may induce memory alterations and often confusional states in aged parkinsonians. Dopamine agonists are prescribed as adjuvant therapy in the treatment of the late side-effects of levodopa. New drugs (selegiline), new pharmaceutical preparations (sustained release forms), the first treatment of the disease (levodopa alone versus agonists alone versus levodopa + agonists), together with the new pharmacological approaches (brain grafts, drug infusions) are now under clinical evaluation.
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PMID:[Antiparkinsonian drugs]. 256 51

The etiology, pathophysiology, diagnosis and clinical presentation, and clinical management of Parkinson's disease are reviewed. The cause of Parkinson's disease, a progressive, degenerative neurologic motor disorder, is unknown. Both endogenous and environmental factors appear to play a role. The clinical features of parkinsonism result from a depletion in dopaminergic transmission in the corpus striatum; the dopamine deficiency is caused by a loss of melanin-containing nerve cells within the substantia nigra and locus ceruleus. In the remaining neurons, hyalin-like masses called Lewy bodies increase in number, but the importance of this is unclear. The diagnosis of Parkinson's disease is based on the clinical presentation of the patient, which initially includes sensory complaints of aching pains, paresthesias, numbness, and coldness. As the disease progresses, the four classic symptoms become prominent: tremor, rigidity, bradykinesia, and postural difficulties. Drug therapy is the cornerstone of clinical management of Parkinson's disease, but no treatment has been found that will retard or reverse the disease. Therapy is usually initiated with anticholinergic agents such as biperiden hydrochloride or trihexyphenidyl hydrochloride with or without amantadine. The mainstay of therapy is levodopa, which is used in combination with dopa decarboxylase inhibitors to decrease the peripheral conversion of levodopa to dopamine. Bromocriptine is a dopamine agonist useful in treating Parkinson's disease. Therapy, which must continue for life, eventually becomes less effective or completely ineffective in all patients. Drug therapy has improved greatly the functional ability of patients with Parkinson's disease, but new agents that can extend the length of effective treatment or reverse the disease are needed.
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PMID:Current concepts in clinical therapeutics: Parkinson's disease. 353 Jun 16

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

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.
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PMID:Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. 613 May 56

CDP-choline, an intermediate in the phospholipid metabolic pathway supposed to improve the functionality of the dopamine (DA) system, was administered to parkinsonian patients in a double-blind cross-over study versus placebo. All patients were already treated with L-dopa + dopa decarboxylase inhibitor. Clinical evaluations were carried out using the Webster Rating Scale (WRS), the Northwestern University Disability Scale (NUDS) and a semiquantitative rating scale for tremor, rigidity and bradykinesia. CDP-choline treatment showed a significant improvement of rigidity and bradykinesia and a less important amelioration of tremor. NUDS and WRS showed a similar positive result. Comparing the results obtained by placebo, we found that the actual clinical efficacy of CDP-choline regards mainly bradykinesia and rigidity (23 and 33% improvement, respectively). The positive effect of CDP-choline on parkinsonian patients already treated with L-dopa + dopa decarboxylase inhibitor stands for a possible action on the DA receptor through an activation of the phospholipid metabolism.
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PMID:New strategies in the management of Parkinson's disease: a biological approach using a phospholipid precursor (CDP-choline). 716 83


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