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. The effect of various agents injected into the cerebral ventricles of the mouse, upon the tremor and hypothermia produced by oxotremorine (0.5 mg/kg i.p.) was studied. 2. Acetylcholine (0.1-10 mug) produced a dose-dependent potentiation of oxotremorine tremor in contrast to the multiphasic effect it had on the accompanying hypothermia. Both tremor and hypothermia were antagonised by very small doses (0.1-10 ng) of atropine. 3. Dopamine and apomorphine (0.1-10 mug) had no significant effect on oxotremorine tremor. A dose-dependent potentiation of hypothermia was, however, observed. 4. Noradrenaline (0.1-10 mug), phentolamine and propranolol (0.1-10 mug) produced no significant effect on tremor and inconsistent results were obtained on hypothermia. 5. Neither tremor nor hypothermia were affected by 5-hydroxytryptamine (1-20 mug). 6. Oxotremorine tremor appears to be due solely to the activation of cholinergic pathways, whereas the production of hypothermia is brought about via a system involving both cholinergic and dopaminergic components. 5-Hydroxytryptamine is not involved.
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PMID:Modification of oxotremorine tremor and hypothermia by injections of drugs into the cerebral ventricles of the mouse. 101 35

Eighteen patients with parkinsonism were treated with a combination of L-dopa and peripheral decarboxylase inhibitor, L-alphahydrazinomethyldopa (MK-486). Modification of L-dopa effect by MK-486 was also studied in parkinsonian patients as well as in cats. (1) Concentrations of dopa and dopamine in plasma and brain were measured in cats following intraperitoneal injection of L-dopa alone (100 mg/kg) or combined with MK-486 (10 mg/kg). Dopa levels in plasma and brain in the combination with MK-486 were three times as high as in L-dopa alone. Dopamine levels in caudate nucleus and putamen were increased nearly fourfold with the combination. (2) Plasma dopa and dopamine levels were measured in parkinsonian patients. Clinical pharmacological studies disclosed that a 1 : 10 ratio of MK-486 to L-dopa in dosage was preferable. (3) Maximum plasma dopa levels with the combination were four times those following L-dopa alone. Plasma dopa sustained a high level over a period of five hours. MK-486 markedly reduced plasma levels of dopamine. (4) There was no significant difference in dopa and dopamine levels in cerebrospinal fluid between L-dopa alone and a combination of MK-486, but dopamine levels in the CSF were still high at four hours after the combination of MK-486. (5) In clinical studies of eighteen patients with parkinsonism, the effectiveness of the combination therapy (mean dosage of L-dopa: 750 mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 15 (67%) with akinesia, in 12 cases out of 17 (71%) with rigidity and in six cases out of 14 (43%) with tremor. Maximum plasma dopa levels were higher in those cases with marked improvement, and were highest in patients with diskinesias as a side effect. (6) An addition of vitamin B6 did not show adverse effects. (7) Transient nausea and vomiting as a side effect, less severe than those experienced with L-dopa alone, were noted in five cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in six cases (33%). These dyskinesias were seen in a high percentage of cases with marked improvement and were never observed in the extremities contralateral to the side of thalamotomy.
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PMID:L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism. 115 13

1 A simple method of injecting soluble substances into the lateral ventricle of the brain of the conscious mouse is described. 2 The effect of various doses of noradrenaline, dopamine, acetylcholine, 5-hydroxytryptamine given into the right lateral brain ventricle were tested on locomotor and exploratory activities of mice. 3 Noradrenaline in a dose of 0.1 mug increased locomotor activity. This effect was prevented by phenoxybensamine but not by propranolol. 4 Higher doses of noradrenaline (1 or 10 mug) decreased locomotor and exploratory activities. Propranolol but not phenoxybenzamine abolished these effects. 5 Dopamine (0.1 or 1 mug) increased locomotor activity. The higher doses also induced tremor. 6 The highese dose of dopamine tested (10 mug) elicited stereotypical behaviour. 7 All the behavioural phenomena induced by 0.1 mug and 10 mug of dopamine were blocked by pimozide. 8 Acetylcholine (1 and 10 mug) and 5-hydroxytryptamine (1 mug) inhibited locomotor and exploratory activity. 9 The effects of 1 and 10 mug of acetylcholine were abolished by atropine (5 mg/kg i.p. Methysergide (5 mg/kg i.p.) had no influence on the effects of 5-hydroxytryptamine (1 mug).
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PMID:Behavioural changes induced in conscious mice by intracerebroventricular injection of catecholamines, acetylcholine and 5-hydroxytryptamine. 120 22

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.
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PMID:Initiating treatment of Parkinson's disease. 134 9

Associations between hyperthyroidism and Parkinson disease have been reported. The treatment of the hyperthyroid state seems to improve the extrapyramidal symptomatology. We report a case of a woman suffering from Parkinson disease and hypothyroidism. The treatment with thyroxine increased parkinsonian tremor. Dopamine regulation of TSH circadian and pulsatile release is not clear. These observations stress the possible role of thyroid hormones in regulating dopaminergic metabolism.
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PMID:[Dysthyroidism and Parkinson's disease]. 222 22

The hypothesis that placental secretion of progesterone (P4) and ovine placental lactogen (oPL) are controlled through different mechanisms was tested. Placental tissue was obtained at days 133-138 of pregnancy, and explant incubations were established using 200 mg tissue per flask in 5 ml O2-saturated DMEM containing 24 mM HEPES and lacking phenol red (pH 7.4). Following a 30-min preincubation, and a 15-min control period, test substances were added and incubations continued, with periodic gassing, for 4 h at 37 degrees C in a shaking water bath. Dopamine (DA), norepinephrine (NE) and epinephrine significantly stimulated P4 production (P less than 0.05). The enhancement of placental P4 production was mimicked by the addition of 8-bromo-cyclic adenosine monophosphate and forskolin (P less than 0.05). The response to catecholamines was abolished by the addition of propranolol (P less than 0.05) but not by phentolamine (P greater than 0.05). Inclusion of a membrane-permeant substrate for P4 synthesis, 25-hydroxycholesterol, increased basal (P less than 0.05) but did not enhance agonist-induced P4 production (P greater than 0.05). High performance liquid chromatographic analysis of placental tissue demonstrated the presence of DA (80.8 +/- 7.07 pg/mg) and NE (48.8 +/- 5.77 pg/mg), as well as catecholamine metabolites. Addition of 1,2-dioctanoyl-sn-glycerol (DAG) or phorbol 12-myristate-13-acetate (PMA) enhanced oPL secretion (P less than 0.05) without affecting P4 production. The response to DAG and PMA, representing the release of considerably more oPL than can be detected by extracting the tissue, was not influenced by treatment with cycloheximide (P greater than 0.05) indicating that secretion of preformed oPL is regulated by the protein kinase C pathway. These results support the hypothesis that the secretion of oPL and the production of P4 are controlled by different mechanisms.
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PMID:Differential control of placental lactogen release and progesterone production by ovine placental tissue in vitro. 223 15

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.
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PMID:Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. 230 73

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

There are a number of different relationships among aging, psychosis and movement disorders, most of which have been proposed to involve the neurotransmitter dopamine. Dopamine content and dopamine receptors have been shown to decrease with age, which may relate to the time of onset of different motor and psychotic disorders, as well as to the appearance of these disorders. For example, some so-called senile movement disorders, such as senile tremor and senile chorea, may relate to alterations in dopaminergic transmission with age, as might the general findings of increased slowing of movements and mildly increased rigidity with age, although it is not clear how common some of these changes are in the medically healthy elderly. Decrease in dopamine with age may also be associated with the findings that choreiform and psychotic disorders (which have been proposed to be related to excess dopaminergic activity) tend to predominate at younger ages, whereas parkinsonism is more common at later ages. Certain findings support this notion, such as the appearance of both dyskinesia and psychosis in patients treated with L-dopa, the finding that psychosis may be less common in patients with later-onset Huntington's disease, and the fact that neuroleptic-induced parkinsonism is often more severe in the elderly. However, the situation is more complicated than this, because there are a number of phenomena that do not fit the pattern, including the observation of an increased incidence of tardive dyskinesia in the elderly. Age-related changes in other transmitters are undoubtedly important in both movements disorders and psychosis, and even dopamine has been proposed to have both trophic and toxic properties over the aging process. In general, care is warranted in the use of any psychotropic medications in the elderly, because there can be widespread and often unpredictable effects of these drugs on both motor and mental function.
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PMID:Association of psychosis and movement disorders in the elderly. 289 37

Dopamine (DA) metabolism and the response to dopaminergic drugs were studied in quaking (QK) mice with neurological mutation expressed in demyelinization of the brain neurons and constant shaking. It has been shown that apomorphine in a low dose (0.25 mg/kg) produced a more significant decrease in locomotor activity in Qk than in control mice. Qk mice appeared to be less sensitive to the blockade by haloperidol of apomorphine (2.5 mg/kg)-induced climbing. DA1 receptor agonist, SKF-38393 caused less pronounced climbing in Qk mice than in the control. There were no changes in DA level in striatum and n. accumbens, whereas 3,4-dihydroxyphenylacetic acid in n. accumbens and homovanillic acid level in striatum were elevated. It was suggested that the increased DA metabolism and the altered sensitivity of pre- and postsynaptic DA receptors are involved in the shaking behaviour of Qk mice.
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PMID:[Characteristics of the brain dopamine system in mice carrying the quaking neurological mutation]. 326


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