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)

There is both experimental and clinical evidence to suggest a role for 5-hydroxytryptamine (5-HT) in Parkinson's disease. The effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinsonian symptomatology was investigated in 10 patients in a single-blind placebo-controlled study. Akinesia and gait improved significantly in a dose-dependent manner in 5 and 7 patients respectively. However there was no significant improvement in tremor. The effects of ritanserin on akinesia and gait are consistent with a role for 5-HT in Parkinson's disease.
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PMID:Effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinson's disease. 134 70

Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice have been studied in order to determine the change in the neurotransmitter profile of the following areas of the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system (LS; tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and cerebellum (CER). Subcutaneous administration of MPTP (40 mg/kg) caused behavioural syndromes including restlessness, straub tail, hindlimb abduction, tremor, jumping, bradykinesia and akinesia in Balb/c mice. There existed a well-defined biphasic profile of motor activity comprising of an initial excitatory phase followed by an inhibitory phase lasting about two and a half and five hours, respectively. A significant rise in 5-hydroxytryptamine (5-HT) content together with a decreased 5-HT utilization as evidenced by lower 5-hydroxyindole acetic acid (5-HIAA) to 5-HT ratio in the above brain areas demarcated the excitatory phase, whereas the inhibitory phase was distinguished by a significant decrease in dopamine (DA) content along with an increased turnover of the amine as shown by a higher homovanillic acid (HVA) to DA ratio in the functionally important nuclei of the extrapyramidal system like SN, NCP and LS. Methysergide, a nonspecific 5-HT receptor blocker, but not ketanserin, a specific 5-HT2 antagonist, prevented the occurrence of the initial excitatory phase without affecting the depressive phase. Administration of apomorphine, a dopamine agonist, 30 minutes prior to MPTP was ineffective, whereas its application 90 minutes after MPTP prevented the occurrence of bradykinesia and akinesia. Interestingly, treatment with haloperidol, the dopamine (D1/D2) antagonist, before and after MPTP administration caused an early onset and prolongation of the inhibitory phase without affecting the initial hyperexcitement. The results provide direct evidence for the involvement of serotoninergic and dopaminergic mechanisms in the genesis of the early and late syndromes of acute MPTP poisoning respectively.
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PMID:Dissociation of serotoninergic and dopaminergic components in acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. 135 Apr 96

In 38 old aged parkinsonian patients, two major subgroups could be established: one with predominant akinesia, rigidity, postural instability and accompanying cognitive impairment with intellectual deterioration correlated with duration of disease but not with age of onset and another with predominant tremor and relatively intact intellectual functions. The mean somatostatin-like immunoreactivity (SLI) level in the cerebrospinal fluid (CSF) was significantly lower in parkinsonian patients (21.4 +/- 8.1 fmol ml-1) compared to senile control patients (29.5 +/- 9.4 fmol ml-1). In contrast to senile dementia of Alzheimer's type SLI was not correlated with dementia scores but with motor disease progression. Homovanillic acid (HVA) significantly decreased only in patients without L-DOPA treatment. Correlations between SLI, HVA and 5-hydroxyindole acetic acid (5-HIAA) indicate a degeneration of multiple neuronal networks which includes somatostatinergic neurons.
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PMID:Parkinson's disease and dementia: clinical and neurochemical correlations. 137 66

In 1817, the English physician, James Parkinson, described the classical symptoms of a disease that was characterized by tremor, rigidity and akinesia. In 1861, the first autopsy of a patient with Parkinson's disease was carried out. Although Ordenstein, a pupil of Charcot, introduced treatment with belladonna in 1867, this later fell into disuse. In 1875, Brissaud determined that the lesion responsible for Parkinson's disease must be locatec the subthalamic regions of the brain. He was also the first to discuss arteriosclerosis-induced forms of Parkinson's disease. In 1919 Tretiakoff discovered cellular damage in the substantia nigra of patients with the encephalitic form of Parkinson's disease. In the 1920s, C. and O. Vogt discovered the basic histological conditions underlying the function of the corpus striatum; later Hassler significantly expanded and completed this work. The following chronology of dates and events is aimed at creating an understanding of the historical aspects of this diseases and consists of milestones in the development of antiparkinsonian treatment.
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PMID:The history of drugs for the treatment of Parkinson's disease. 149 Dec 42

Zonisamide is a new antiepileptic drug which has a wide range of antiepileptic efficacy. This drug is becoming widely to be used for patients with refractory epilepsies. The author reports two patients who developed resting and postural hand tremor after administration of zonisamide. The tremor was confined to the upper extremities and was enhanced with the emotional stress. The tremor has 4-5 Hz frequency and was severe enough to disturb their daily activities. Mild cogwheel rigidity was seen, but neither akinesia nor gait disturbance was recognized. The symptoms disappeared completely after cessation of the drug. This side effect should always be kept in mind in the treatment with zonisamide.
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PMID:[Zonisamide induced tremor--report of two cases]. 156 87

The neurologic states and activities of daily life of patients with Parkinson's disease were evaluated using a rating scale with subitems, and subsequently the neurologic disturbance scores and the daily activity impairment scores were obtained. Subjects consisted of 19 normal controls, and 55 ambulatory patients without marked dyskinesia who were on various anti-parkinsonian drugs. Blink reflex was elicited by paired electrical stimulation over the supraorbital nerve. The interval time between the conditioning stimulation and the test stimulation was set at 200 ms, and 5 serial ipsilateral maximal R2 amplitudes on the stimulated side were measured. The mean of the paired maximal R2 amplitude ratio (test/conditioning), expressed as a percentage, was defined as the habituation index. The habituation indices in normal controls and those with Parkinson's disease were 17.1 +/- 7.6 and 51.9 +/- 29.3, respectively (P less than 0.01). The degree of akinesia, rigidity, balance/gait and dysarthria was positively correlated with the habituation index (P less than 0.01), while tremor was not. On the whole the habituation index was found to have a significant correlation not only with the neurologic disturbance score but also with the daily activity impairment score (P less than 0.01).
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PMID:A correlation study between blink reflex habituation and clinical state in patients with Parkinson's disease. 156 13

The causes of symptomatic parkinsonism are enumerated and discussed including drug-induced, vascular, toxic, postencephalitic and posttraumatic parkinsonism. The environmental hypothesis and the concept of oxidative stress in the pathogenesis of Parkinson's disease are illustrated. The clinical diagnosis, the differential diagnosis and the possible diagnostic errors originating from the cardinal symptoms akinesia, rigor und tremor in the early stages of the disease are delineated. At last the contributions of EEG, CCT, evoked potentials, MRI, PET und the apomorphine test to the diagnosis especially early diagnosis are evaluated.
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PMID:[Current aspects in diagnosis of Parkinson disease]. 158 88

Abnormally increased subthalamic nucleus output to the internal pallidal segment and the reticular part of the substantia nigra plays a critical pathophysiological role in the development of parkinsonism. Because synaptic transmission of subthalamic output is glutamatergic and mediated, in part, by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, AMPA receptor antagonists may possess antiparkinsonian properties. We report that in monoamine-depleted rats, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) (Novo-Nordisk, Copenhagen, Denmark)--a selective antagonist of the AMPA subtype of glutamate receptor--suppressed muscular rigidity but had no effect on akinesia. NBQX microinjected into the subthalamic nucleus, internal pallidal segment, and reticular part of the substantia nigra, but not into the laterodorsal neostriatum of the rats, stimulated locomotor activity and reduced muscular rigidity. In aged Rhesus monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, intramuscular NBQX produced clinically apparent improvement in akinesia, tremor, posture, and gross motor skills. NBQX also potentiated the antiparkinsonian effects of L-3,4-dihydroxyphenylalanine in both rats and monkeys. Blockade of excitatory synaptic transmission by AMPA receptor antagonists may provide a new therapeutic strategy for Parkinson's disease (PD).
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PMID:The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. 166 77

The introduction of levodopa in the treatment of Parkinson's disease had modified both the prognosis and the current concepts of the disease, Although levodopa remains the most potent drug for the treatment of Parkinson's disease, its long-term use is associated with fluctuations in motor performance, abnormal movements and psychotic hallucinations. These late side-effects remain difficult to treat and thus raise questions as to the benefits and risks of first-time treatment with levodopa. Levodopa mainly alleviates akinesia and rigidity and to a lesser extent, tremor. Levodopa increases life expectancy. This paper reviews some recent developments in the pharmacology of Parkinson's disease. Recent findings indicate that not only central dopamine but also several other central neurotransmitter and receptor changes are involved in the pathophysiology of Parkinson's disease. New data on autonomic dysfunction in Parkinson's disease are presented. New methods of investigation (clinical rating scales, pharmacological tests, imaging techniques, etc.) are reviewed. Finally, future strategies, e.g. the development of potent new symptomatic drugs (selective D2 and D1 agonists, new formulations of apomorphine, COMT inhibitors, new routes of administration, etc.) and etiopathogenic agents (antioxidative and anti-free radical drugs, etc.) are discussed.
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PMID:Recent advances in the clinical pharmacology of Parkinson's disease. 168 24

Few parkinsonian patients present with 'pure akinesia' or with severe akinesia accompanied by only mild rigidity, tremor and other manifestations such as ophthalmoplegia. Pathological examinations of such cases have rarely been conducted and have revealed findings compatible with progressive supranuclear palsy (PSP), pallido-nigro-luysian atrophy (PNLA) or Parkinson's disease. We report a parkinsonian patient whose main clinical feature was akinesia. A postmortem study of this patient showed findings corresponding to PNLA and PSP. Histochemical properties of the pallidal pigment granules were equivalent to those of Hallervorden-Spatz disease (HSD) and striatonigral degeneration. In addition to iron-positive pigment granules, spheroids, severe neuronal loss and gliosis in the globus pallidus and substantia nigra, formation of Alzheimer's neurofibrillary tangle (NFT) in the brainstem shares characteristics with PSP, adult onset HSD and PNLA. We suggest that the underlying pathology of 'pure' akinesia is most often situated in the globus pallidus substantia nigra and subthalamus (Luys), and that PSP, PNLA and adult onset HSD may constitute a spectrum of one disease.
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PMID:Pallido-nigro-luysian atrophy, progressive supranuclear palsy and adult onset Hallervorden-Spatz disease: a case of akinesia as a predominant feature of parkinsonism. 170 2


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