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)

The clinical pattern of symptoms consists of motor disorders (akinesia, tremor, rigor), emotional disorders (depression, abnormal behaviour), autonomic disorders (sweating, salivation, seborrhoea, constipation) and intellectual disorders (bradyphrenia, Alzheimer's dementia)
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PMID:[Clinical picture of Parkinson disease]. 378 88

Guinea pigs were inoculated intracerebrally with cerebrospinal fluid (CSF) and/or brain tissue suspensions from 8 patients with Creutzfeldt-Jakob disease (CJD) and with CSF from 2 patients with Alzheimer's disease. After a very long incubation period (over 360-420 days) a serially transmissible experimental disease appeared in the guinea pigs inoculated with CSF from 5 of the CJD patients, with either CSF or brain suspension from one CJD patient and with brain suspensions from the remaining 2 CJD patients. The disease was characterized by tremor, ataxia, convulsions and morphopathological lesions, such as spongiform change, glial hyperplasia and vacuolation of the neurons. Inoculations of CSF from the two Alzheimer's disease cases gave negative results.
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PMID:Data on the experimental transmission in the guinea pig of some human chronic degenerative diseases: Creutzfeldt-Jakob and Alzheimer's disease. 391 53

It must be recognised that patients with idiopathic Parkinson's disease will eventually get worse and, where appropriate, realistic prognostications of the future should be conveyed to patients and their responsible relatives. Some 15 per cent of patients will not respond to levodopa. When a patient does not show a significant improvement on therapy a number of important questions should be considered. Is the diagnosis correct? Consider an alternative diagnosis such as progressive supranuclear palsy, drug effect, multi infarct dementia, Alzheimer's disease, striatonigral degeneration, senile or essential tremor and the Shy-Drager syndrome which all may be mistaken for Parkinson's disease. Is the patient complying with therapy? Is the dose adequate and the frequency of administration appropriate? Are the symptoms caused by drug therapy? Would the addition of other therapy assist, for example amantadine, anticholinergics or bromocriptine? Is the patient on other drugs which may be contributing to the impaired function? Is the patient depressed? Is there some other underlying condition aggravating the Parkinson's disease?
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PMID:Difficulties in long term management of Parkinson's disease. 649 65

Clinical and neuropsychological findings, EEG, and several blood and CSF parameters were investigated in 36 patients with Alzheimer's disease (AD) and 35 patients with senile dementia of Alzheimer type (SDAT). There were more women among senile patients and more familial cases among presenile patients. The average duration of the symptoms was longer in presenile patients (6.1 years) than in senile patients (3.9 years). This could be due to the lower resistance to the disease process in the senile group. Extrapyramidal signs, especially rigidity, were found in over 60% of all patients and in practically all patients with advanced dementia. Tremor was found in three patients only. Four presenile (11%) and two senile (6%) patients had epileptic seizures. All patients had abnormal EEG recordings, mainly in form of diffuse slowing. A positive correlation was found between the EEG abnormality and the severity of dementia in AD but not in SDAT. However, the difference between the correlation coefficients in AD and SDAT was insignificant. Between EEG and the duration of the disease there was no correlation. EEG was not more abnormal in very severe dementia than in severe dementia. Other findings were similar in AD and SDAT. It is concluded that it is artificial to separate AD and SDAT at the age of 65 and that they clinically compose a single entity. This entity could well be called Alzheimer's disease.
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PMID:Alzheimer's disease and senile dementia of Alzheimer type. A comparative study. 711 68

2,8-Dimethyl-1-oxa-8-azaspiro[4,5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4,5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's type. The compounds were tested for central muscarinic M1 and M2 receptor affinity and in vivo muscarinic activities: namely, amelioration of scopolamine-induced impairment in rat passive avoidance tasks, and induction of hypothermia, tremor, and salivary secretion. Compound 17 exhibited potent muscarinic activities in vitro and in vivo with no selectivity. Systematic modifications of 17 were conducted, and a number of compounds, including the 2-ethyl analogue (18), 3-methylene analogue (29), 3-dithioketal analogues (26, 28), and 3-oxime analogue (37) were found to display preferential affinity for M1 receptors over M2 receptors and, in addition, to exhibit potent antiamnesic activity sufficiently separated from hypothermia-inducing activity, taken as an index of cholinergic side effects, compared with the reference compound RS86 (1). Structure-activity relationships are discussed in comparison with those for muscarone analogues. Of these compounds only two, 2-ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one (18) and 2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (29), stimulated phosphoinositide hydrolysis in rat hippocampal slices, indicating partial agonistic activity for M1 muscarinic receptors. The optical resolution of 18 and 29 was performed. Eudismic ratios of both compounds in binding affinity were low, but M1 agonist activity resided preferentially in the (-)-isomers. The absolute configuration of (-)-29 was determined by X-ray crystal structure analysis to be S, being the same as that of muscarone. Based on the in vivo selectivity, (-)-29 was selected for clinical studies.
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PMID:Synthesis and structure-activity studies of a series of 1-oxa-8-azaspiro[4.5]decanes as M1 muscarinic agonists. 755 70

The authors examined the presence of significant regional cerebral blood flow (rCBF) differences between Alzheimer's disease (AD) patients with and without extrapyramidal signs (EPS). Nine patients with probable AD and EPS (resting tremor or rigidity and bradykinesia) and 9 AD patients without EPS, comparable in age, duration of illness, and global cognitive decline, were studied with [99mTc]HMPAO SPECT. Patients with AD and EPS showed significantly lower rCBF in the superior frontal, superior temporal, and parietal regions of the left hemisphere than AD patients without EPS. Rigidity and bradykinesia independently accounted for the decreased rCBF in these areas. These findings suggest that the presence of EPS in AD may result from dysfunction in specific brain regions.
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PMID:A SPECT study of parkinsonism in Alzheimer's disease. 758 Jan 89

CI-979 ((E)-1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxaldehyde, O-methyloxime monohydrochloride), a novel muscarinic agonist, is being investigated as a potential treatment for Alzheimer's disease (AD). The objective of the present study was to determine the safety and tolerance of multiple, rising, oral doses of CI-979 in patients with AD. Ten male patients aged 59 to 74 years (mean 65 years) who met NINCDS criteria for AD were randomized to receive either CI-979 (eight patients) or placebo (two patients) according to a double-blind, parallel-group, rising-dose design. Doses were 0.5-mg q6h, 1-mg q12h, 1-mg q6h, 2-mg q12h, 2-mg q6h, 2.5-mg q6h, and 3-mg q6h. All doses were to be administered sequentially for 3 days each with the exception of the 2.5-mg q6h dose, which was to be administered for 1.5 days. Five patients receiving CI-979 discontinued study medication because of adverse events; two after receiving 2-mg q6h (10 doses), two after 2.5-mg q6h (5 doses), and one after 3-mg q6h (4 doses). The study was terminated following administration of the fourth 3-mg dose due to the nature and intensity of adverse events. Cholinergic symptoms including diaphoresis, hypersalivation, nausea, diarrhea, hypotension, chills, headache, flatulence, and urinary frequency and signs suggestive of parkinsonism (cogwheeling, tremor, pillrolling, posturing, and shuffling gait) were dose-limiting. The frequency and intensity of adverse events increased with increasing CI-979 dose. No other clinically significant CI-979-related changes occurred in physical examinations, clinical laboratory measurements, electrocardiograms, or ophthalmologic examinations. Steady-state trough plasma CI-979 concentrations increased in proportion to dose. In summary, CI-979 doses of 1-mg q6h were well tolerated by all patients; 2-mg q6h was tolerated by most patients, and 2.5-mg and 3-mg doses were poorly tolerated, Dose titration to a maximum of 2-mg q6h will therefore be used in initial efficacy trials of CI-979 in patients with AD.
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PMID:Safety and tolerability of CI-979 in patients with Alzheimer's disease. 762 16

We postulate that the effect of cholinesterase inhibitors to ameliorate the cholinergic deficit in Alzheimer's disease is related to their ability to maintain long-lasting, non-toxic steady-state levels of acetylcholine in cortex. We investigated the effect of the cholinesterase inhibitor, MDL 73,745 (2,2,2-trifluoro-1-(3-trimethylsilylphenyl)ethanone), on the extracellular levels of acetylcholine, norepinephrine, dopamine and 5-hydroxytryptamine in the cerebral cortex of the rat by high-performance liquid chromatography coupled with electrochemical detection. The drug significantly increased acetylcholine levels above the baseline at 2 and 10 mg/kg s.c., but not at the 1 mg/kg dose. At both 2 and 10 mg/kg there was a good correlation between cholinesterase inhibition and acetylcholine increase in cortex. At the 2 and 10 mg/kg doses, the maximal cholinesterase inhibition was 64% and 77%, respectively, and the increase in acetylcholine release was 481% and 1016%, respectively. Norepinephrine and dopamine, but not 5-hydroxytryptamine levels, were also significantly increased by the 10 mg/kg dose. The increases of norepinephrine and dopamine levels reached a maximum of 124% and 370%, respectively, and continued for a period of at least 8 h. Cholinergic side-effects were most marked at the 10 mg/kg dose but were also noticeable at the 2 mg/kg dose in the form of fasciculations, tremor and splay.
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PMID:Effect of MDL 73,745 on acetylcholine and biogenic amine levels in rat cortex. 778 1

Studies of extrapyramidal motor function in patients with schizophrenia have contributed to our understanding of the phenomenology and therapeutic outcome associated with neuroleptics. An increasing body of literature suggests that extrapyramidal motor abnormalities associated with schizophrenia may be linked to the pathophysiological mechanisms responsible for schizophrenia. Similarly, it has been documented that the extrapyramidal system may be involved in motor abnormalities in patients with Alzheimer's disease (AD). The present study was undertaken to examine motor function in schizophrenia and AD patients with psychosis. Quantitative instrumental procedures were used to examine rigidity, tremor, and bradykinesia in 13 neuroleptic-naive patients with schizophrenia, 13 AD patients with psychosis, and 26 age-comparable controls. Both schizophrenia and AD patients had significantly higher tremor and rigidity scores than did normal subjects. This comparative study of schizophrenia and AD patients with psychosis suggests that the effect of dementia in patients with psychosis is to prolong movement time, whereas abnormal parkinsonian postural tremor tends to be associated with psychosis in the absence of dementia.
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PMID:Extrapyramidal motor abnormalities associated with late-life psychosis. 790 62

Parkinson's disease is a progressive neurodegenerative condition of unknown cause and with no known cure. The diagnosis is based on clinical findings of rest tremor, muscle rigidity, bradykinesia, and gait instability. Over 40% of patients develop a dementia syndrome that is largely distinct from Alzheimer's disease. Depression is common, also occurring in more than 40% of patients with PD. Careful evaluation in necessary to help distinguish Parkinson's disease from secondary causes of parkinsonism. Carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B inhibitors are the mainstays of treatment. Anticholinergics and other agents may also be useful. Pharmacologic treatment must be carefully titrated to control symptoms and to avoid side effects. In advanced disease, dose-related dyskinesias, end-of-dose wearing-off effect, and unpredictable sudden motor fluctuations become very disabling and difficult to manage.
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PMID:Parkinson's disease: making the diagnosis, selecting drug therapies. 792 45


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