Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.
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PMID:Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. 218 10

Akinesia refers to failure of willed movement to occur, and bradykinesia refers to slowness of movement that is ongoing. One mechanism of bradykinesia is failure to energize muscles up to the level necessary to complete a movement in a standard amount of time. Akinesia may occur for two possible reasons. One is that the movement is so slow (and so small) that it cannot be seen. A second is that the time needed to initiate the movement becomes excessively long; this can be studied by evaluation of reaction time. One simple factor in prolongation of reaction time is present in patients with rest tremor, who appear to have to wait for a beat of tremor in the agonist muscle of the willed movement in order to initiate the movement. Reaction time studies in patients with Parkinson's disease demonstrate that simple reaction time is delayed, while choice reaction time is normal. Additionally, there does not appear to be any slowness of thinking or difficulty with storage of a motor program. Hence, the difficulty with reaction time in these patients appears to be the time that it takes to execute a motor program. Studies with magnetic stimulation of the motor cortex during the reaction time period seem to support this hypothesis. Slowness of activation of the motor cortex to trigger a movement may well be analogous in mechanism to the slowness of bradykinesia.
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PMID:Clinical neurophysiology of akinesia. 226 21

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.
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PMID:The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography. 228 39

Treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1-4 mg/kg for up to 4 days) caused a profound parkinsonian state. Ten days from the start of MPTP treatment, all animals showed marked motor impairment, consisting of bradykinesia and akinesia, limb rigidity, postural abnormalities, loss of vocalisation and blink reflex, and, on occasions, postural tremor. Measurement of caudate-putamen monoamine content at this time showed a profound loss in 3,4-dihydroxyphenylethylamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations. Measurement of neuropeptide concentrations in the caudate-putamen, internal and external segments of the globus pallidus, nucleus accumbens, substantia nigra, frontal cortex, and hippocampus showed met-enkephalin, leu-enkephalin, and cholecystokinin (CCK-8) concentrations to be unaffected by MPTP treatment. There was a small decrease in the substance P content of frontal cortex, but otherwise the content of this neuropeptide was unaltered. Parkinsonism in the marmoset, induced by MPTP treatment 10 days earlier, does not alter neuropeptide concentrations in the manner observed in Parkinson's disease.
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PMID:Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of the common marmoset. 242 37

Flunarizine hydrochloride (FZ), a calcium entry blockade, has been used nationwide in Japan as a cerebral active vasodilator since October, 1984. The present paper reports 31 cases of FZ-induced Parkinsonism, depression and akathisia, referred to our hospital between October 1986 and September 1988. Out of the 31 patients, four including two with Parkinson's disease and one each with progressive supranuclear palsy and olivopontocerebellar atrophy showed worsening of their parkinsonian symptoms within a few months after FZ administration. The remaining 27 patients (7 males and 20 females) newly developed Parkinsonism after treatment with FZ. Symptoms appeared one week to two years (mean: 6.1 months) after starting FZ of a daily dose of 10 mg. FZ had been used in 6 patients for cerebrovascular episodes confirmed by clinical history or brain CT, and in the remainder, for dizziness, light-headedness, hypertension, amnesia or hypochondric neurotic complaints. Akinesia and bradykinesia progressed rather rapidly after onset, and patients became unambulatory within several months. Symptoms had worsened, and L-dopa, anticholinergic drugs, and bromocriptine had been ineffective until FZ was discontinued. Their Parkinsonism was characterized by marked akinesia, bradykinesia, and moderate rigidity. Masked face was seen in most of them. Tremor was absent at rest, and induced in 12 patients by posture and/or action. Sixteen patients were accompanied by depression, and five, by akathisia. Improvement began several weeks after withdrawal of FZ, and most patients recovered almost completely within a few months although mild rigidity and bradykinesia remained in some.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parkinsonism, depression and akathisia induced by flunarizine, a calcium entry blockade--report of 31 cases]. 258 81

Saccadic eye tracking was studied in a monkey given i.v. injections of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The Parkinson-like symptoms which appeared in the animal's general motor behavior (akinesia, bradykinesia, hypokinesia) were also observed in its eye tracking. Similar oculomotor deficits are seen in patients with idiopathic Parkinsonism. The MPTP model offers excellent possibilities for studying the mechanisms underlying the motor disabilities of Parkinson's disease.
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PMID:Saccadic eye movement deficits in the MPTP monkey model of Parkinson's disease. 302 Dec 80

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a potent dopaminergic neurotoxin, was administered to cats systemically for 5 to 7 days. This treatment produced a behavioral syndrome characterized by akinesia, ataxia, bradykinesia, and feeding difficulties, lasting for several weeks. During this period of severe behavioral impairment, caudate and nucleus accumbens dopamine and norepinephrine concentrations were quite depleted. Behavioral recovery ensued over the next several weeks as did some recovery of striatal catecholamines. MPTP destroyed the majority of substantia nigra pars compacta neurons while affecting a much lesser number of locus ceruleus and ventral tegmental neurons. These results demonstrated for the first time that MPTP can cause long-lasting deficits in nigrostriatal functioning in the cat and may provide a means for studying the apparently selective neurotoxic effects of MPTP as well as for understanding the pathophysiology of Parkinson's disease.
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PMID:Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry. 348 7

Nine monkeys (Macaca fascicularis) were used in this study. Four monkeys were rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 0.5 mg/kg intravenously. Three animals were injected once daily for 4 days, and one animal once weekly for 4 weeks. Five animals were used as controls. All MPTP-treated animals demonstrated the same clinical features which included akinesia, bradykinesia, a flexed posture of the trunk and all extremities, decreased initiation of the threat response, decreased vocalization and difficulty in swallowing. An increase in rigidity and reflexes was noted in all extremities. Tremor was present in all animals. Determination of the local spinal metabolic rate of glucose (LSMRg) utilization revealed an increase (P less than 0.05) in LSMRg in Rexed layer I in all cord segments and in Rexed layer II in both cervical and lumbar segments. Rexed layer X demonstrated a significant (P less than 0.05) increase in LSMRg at the cervical cord. The LSMRg in the animal that received weekly injections was similar to the daily injected animals.
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PMID:Spinal cord metabolism of the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-treated monkey. 387 82

The long-term effects of bromocriptine as an adjuvant were investigated in 32 patients (20 male, 12 female), aged 43-76 years (mean 65.4), suffering from parkinsonism for 3-20 years (mean 9.3). Patients were pretreated with levodopa/decarboxylase inhibitor for 24-116 months (mean 74.9). Bromocriptine was given because of a decline in the response to levodopa, various kinds of "on-off" phenomena, and disabling dyskinesias. Levodopa was reduced by 18%, while bromocriptine was added with a mean dose of 29 mg. The results showed a marked tremor and rigidity response, clearly greater than that of bradykinesia of the hands. The improvement after 4 weeks of bromocriptine treatment was maintained over 12 months. Only gait disturbances tended to increase. At the same time the self-ratings of the patients showed an increase in disability as far as daily activities were concerned. Likewise, the "on-off" symptoms with regard to the wearing-off effects worsened in comparison with the condition during the 4-week period. Akinesia paradoxica was never definitely influenced. An increase in dyskinesias was avoided and serious side-effects could be kept under control.
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PMID:Long-term experience with bromocriptine in advanced parkinsonism. Results after one year's treatment. 618 12

Central to the concept of subcortical dementia is the implication that the increased response latencies, which distinguish the syndrome, are due to a slowing of thought processes. The term 'bradyphrenia' has been applied to this presumed slowing of thought in Parkinson's disease and implies (1) that increased response latencies are not strictly motoric but are due to slowed information processing, and (2) that the mental slowing is analogous to the bradykinesia observed in the motor domain and, hence, attributable to dysfunction of dopaminergic basal ganglia mechanisms. The current study attempts to validate this definition of bradyphrenia by seeking a slowing of thought in Parkinson's disease which can be linked directly to bradykinesia. Six parkinsonian patients with end-of-dose akinesia were studied in three experiments which allowed separation of the speed of specific cognitive operations from the speed of motor responses. Serving as their own controls, they were tested both during the parkinsonian 'off' state, and when bradykinesia was alleviated by drug therapy. Four additional patients with newly diagnosed Parkinson's disease were studied before and following successful treatment with L-DOPA/carbidopa. The first experiment measured the rate of memory scanning, the second examined orientating of attention in the visual fields, and the third measured the time required to prepare a manual movement. The results show that overall reaction time increased when patients were in the untreated state, but without a concomitant slowing of purely cognitive components. The slowing of thought often reported in Parkinson's disease does not necessarily accompany bradykinesia and thus may not be related to dopaminergic dysfunction. These findings emphasize the need for caution in inferring a slowing of thought from increased response latencies in subcortical disorders.
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PMID:Cognition and the basal ganglia. Separating mental and motor components of performance in Parkinson's disease. 650 9


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