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)

Forty patients with severe Parkinson's disease (23 men, 17 women) who had been treated for six years with L-dopa-decarboxylase inhibitor, were part of a placebo-controlled double-blind trial to test the effectiveness of bromocriptin. In all patients the effectiveness of L-dopa had been decreasing, 34 patients had L-dopa-induced dyskinesias, 35 "on-off" symptoms. Bromocriptin dosage was gradually increased to a total dose of 30 - 40 mg daily. This led to a 25% reduction in L-dopa requirements. The symptoms of Parkinson's disease were favourably influenced, with rigor, tremor and also walking disturbances responding better than bradykinesia of the hands. At the same time, there was a marked prolongation of the periods of good mobility ("on" time) from 7 to 10.8 hours without influence on other "on-off" symptoms such as paradoxical akinesia. Two patients had to be excluded from the trial because the treatment caused side effects (orthostatic hypotension, exogenous psychotic symptoms). Other side effects, such as nausea and mild forms of collapse, could be controlled by drugs.
 ...
PMID:[Bromocriptin in the treatment of progressive stages of Parkinson's disease (author's transl)]. 679 66

Our experiments demonstrate that morphine and haloperidol produce two distinct and contrasting behavioral states, which can be thought of as exaggerated, isolated, and simplified forms of organized adaptive behavioral states functioning as components of normal motivated behavior. Haloperidol catalepsy constitutes an organized state in which tonic reactions subserving the maintenance of stable static equilibrium prevail, at the expense of phasic locomotor reactions. In contrast, morphine produces an immobility state characterized by inhibition of the postural support subsystem, and compatible with or preparatory to locomotor rather than static postural reactions. haloperidol-treated rats (1, 2.5, 5, 10 mg/kg i.p.) display exaggeraged bracing reactions to passive displacement as well as to stimuli which do not actively challenge stable equilibrium. In contrast, rats treated with morphine sulfate (10, 20, 40, 80 mg/kg i.p.) show a dose-dependent suppression of bracing and an exaggerated tendency to run in response to stimuli which produce bracing in haloperidol-treated rats. Further evidence that haloperidol-treated rats are organized to stand still in stable equilibrium includes their typical posture during akinesia (i.e. broad-based support), bradykinesia, tonic grasping and enhanced postural components of contact- and air-righting. Under morphine, however, the postural support subsystem is dispensed with, as evidenced by the posture of akinesia (i.e. a frozen phase of the locomotor step cycle associated with loss of limb support), absence of tonic grasping, and nature of the deficits in contact- and air-righting. Furthermore, the opiate-induced immobility state is accompanied by an increased readiness to locomote. Morphine produces an alternation between two extreme behavioral states: complete immobility (inhibition of the postural support subsystem) versus locomotor paroxysms (varying degrees of 'explosive motor behavior'). We suggest that the postures or actions adopted by morphine-treated rats involve movement subsystems concerned with the adaptive behavioral state known as the 'immobility reflex' ('tonic immobility', 'animal hypnosis').
 ...
PMID:Morphine versus haloperidol catalepsy in the rat: a behavioral analysis of postural support mechanisms. 719 46

The administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson-like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4-6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP-treated cats. Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]-mazindol, in the caudate nucleus (64-82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]-SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (> 24%; P < 0.05) of symptomatic cats and in all regions of the caudate-putamen (> 30%; P < 0.05) of recovered animals. [3H]-SCH 23390 binding in the substantia nigra pars reticulata was half of that in the striatum and showed no changes in symptomatic or recovered animals. No alterations in the binding of [125I]-epidepride to D2 receptors was observed in any region of the striatum in either symptomatic or recovered animals. [125I]-Epidepride binding in the SNc was decreased by > 36% (P < 0.05) following MPTP treatment. These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of D1 receptors throughout the striatal complex. The present data also show that direct correlations between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are difficult and that the relationships between DA receptors/transporters and behavior require further study.
 ...
PMID:Alterations in dopamine uptake sites and D1 and D2 receptors in cats symptomatic for and recovered from experimental parkinsonism. 770 43

The potency of felbamate, an anti-convulsive drug, to influence dopamine D1 (SCH 23390) and D2 (haloperidol) receptor-mediated catalepsy (akinesia and bradykinesia) was studied in rats. In the catalepsy test, felbamate antagonized dopamine D2 receptor- but not D1 receptor-induced akinesia. Bradykinesia in the open field was never influenced. The results demonstrate that felbamate has similar anti-parkinsonian potential as glycine site antagonists blocking the N-methyl-D-aspartate (NMDA) receptor complex.
 ...
PMID:Felbamate, an anti-convulsive drug, has anti-parkinsonian potential in rats. 784 5

A predominant symptom of Parkinson's disease is akinesia and bradykinesia, slowing in the initiation and execution of voluntary movement. There has long been speculation as to whether cognitive processes undergo similar processes, but findings may be confounded by the frequent co-occurrence of dementia and/or depression. Mental rotation provides an internal or cognitive analogue of real movement, and enables us to determine the speed of such mental processes independent of any concurrent motor slowing in response initiation and execution. Medicated patients with Parkinson's disease who were free of dementia and depression were found to be able to mentally rotate alphanumeric or figural stimuli, with and without advance information as to the view (front or back) of a stick figure shortly to be shown, as rapidly as normal healthy controls. We conclude that cognitive processes involved in mental rotation are not necessarily slowed in Parkinson's disease.
 ...
PMID:Parkinsonian patients without dementia or depression do not suffer from bradyphrenia as indexed by performance in mental rotation tasks with and without advance information. 787 46

Previous parkinsonian rat models have utilized stereotactic 6-OHDA injections to completely lesion the dopaminergic mesostriatal system on one side. Recently, hemiparkinsonian rat models in which the mesolimbic system is left intact have been developed. The selective, partial lesion models better mimic the neuropathology of human parkinsonism in which there is usually an incomplete destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and a relative sparing of ventral tegmental area (VTA) cell groups. However, such hemiparkinsonian models which possess dopaminergic asymmetry cannot demonstrate bradykinesia, one of the main symptoms in human parkinsonism. Meanwhile, bilateral lesions of the ascending forebrain dopaminergic system have been reported to induce severe aphagia, adipsia and akinesia. We, therefore, undertook development of a bilateral partial SNpc lesion model which also spares the VTA on both sides. We have investigated spontaneous locomotor activities as well as amphetamine, apomorphine and levodopa induced activities during a subchronic period of up to 27 days after the bilateral lesion. Three activity parameters i.e. horizontal activity, vertical activity and distance analyzed. Spontaneous activity was significantly decreased in animals with extensive (> 80%) SNpc lesions on both sides. Animals with a > 95% lesion were severely aphagia and adipsia. Responses to amphetamine and apomorphine were variable. It is possible that in some cases the bilateral SNpc neurons were not equally damaged, which could cause the enhanced rotational behavior. Bradykinetic rats displayed on the average, a > 20% decline in horizontal activity, a > 40% decline in vertical activity and a > 30% decline in distance traveled after the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of bilateral 6-OHDA lesions of the substantia nigra on locomotor activity in the rat. 790 30

The role of the entopeduncular nucleus (EP) and the subthalamic nucleus (STN) in mediating dopamine receptor antagonist-induced catalepsy in the rat was investigated. Five days after bilateral lesions of EP and STN respectively with the excitotoxin quinolinic acid (15, 30 nmol/0.5 microliter/side and 24 nmol/0.5 microliter/side, respectively) rats were injected intraperitoneally with the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) or the dopamine D2 receptor antagonist haloperidol (0.5 mg/kg). Complete EP lesions prevented both SCH 23390- and haloperidol-induced catalepsy. STN lesions exerted pronounced anticataleptic effects in case of haloperidol-induced catalepsy, but less pronounced in case of SCH 233390-induced catalepsy. Further characterization of these anticataleptic effects in an open field demonstrated, that neither EP- nor STN lesions reversed bradykinesia, which occurred after selective dopamine receptor blockade. In conclusion, both EP and STN participate in the mediation of catalepsy induced by dopamine D1- and dopamine D2 receptor antagonists. Thereby these nuclei preferentially mediate rigidity and akinesia, but to a lesser extent bradykinesia.
 ...
PMID:Lesions of the entopeduncular nucleus and the subthalamic nucleus reduce dopamine receptor antagonist-induced catalepsy in the rat. 791 35

Fetal graft research and renewed interest in Leksell's postero-ventral pallidotomy (PVP) stimulated reconsideration of surgical therapy for Parkinson's disease (PD), particularly with regard to improving akinetic symptoms previously thought resistant to surgical lesions. Review of our series and other published results of PVP and fetal graft show that PVP has beneficial effects on both akinetic and hyperkinetic symptoms that better the results reported for fetal graft implantation and other conventional stereotactics. Presented are the results of 60 consecutive patients, 55 of whom underwent PVP, and 5 who underwent fetal graft implantation. Using the Unified Parkinson's Disease Rating Scale (UPDRS), we found that PVP gave significant (P < 0.05) reductions in akinetic symptomatology including freezing, arising from a chair, posture, gait, postural instability, and bradykinesia. Fetal graft patients had significant reductions in two akinetic symptoms: bradykinesia and postural instability. PVP's dramatic therapeutic effects on akinesia may be explained by interruption of amplified collateral inhibitory output from the pallidum to brain stem locomotor centers such as the pedunculopontine nucleus, whereas interruption of collaterals to ventral lateral thalamus by PVP may account for the elimination of hyperkinesia. The excellent results of PVP represent a significant advance in the surgical treatment of PD.
 ...
PMID:Stereotactic pallidotomy results for Parkinson's exceed those of fetal graft. 794 41

Patients with Huntington's disease exhibit poorer-quality handwriting, sometimes clinically exhibiting macrographia, an increase in the size of handwriting. To characterize deficits in handwriting of patients with Huntington's disease, we compared the writing of 12 young, 12 age-matched controls, and 12 patients with Huntington's disease. Subjects were asked to write the letter "l" four times, at a constant length, on a graphics tablet that sampled pen position at 200 Hz. Huntington's disease causes chorea (involuntary movement), akinesia (difficulty in initiating voluntary movement), and bradykinesia (slowness and difficulty in maintaining voluntary movement). To distinguish changes in handwriting quality due to involuntary movement from impairments of voluntary movement, handwriting samples with obvious choreic movements were analyzed separately from other handwriting samples. Several measures of quality of handwriting were considered, based on: the regularity and consistency of handwriting, the efficiency of movement trajectories, and the proportions of movement occurring at specific frequencies. Results suggested that Huntington's disease increases variability of movement parameters, and causes problems in producing smooth movements. Choreic movement was best characterized by the number of zero crossings in the velocity function relative to the prescribed number of writing strokes. We hypothesize that macrographia in Huntington's disease occurs when chorea predominates over bradykinesia. Comparisons were made between the handwriting of patients with Huntington's and Parkinson's diseases.
 ...
PMID:Characteristics of handwriting of patients with Huntington's disease. 799 Aug 47

The akinetic crisis is an "off" state that lasts more than 48 hours with akinesia, rigidity and bradykinesia, occurring with signs of CNS dysregulation in advanced stages of Parkinson's disease. 7 akinetic crises lasting 4 to 14 days (average 9.3) were observed in 744 hospitalizations over a period of 7 years. The age of the patients with akinetic crisis and the mean duration and the severity of the disease were significantly higher than in the other patients. While bradykinesia and rigor are the most relevant clinical signs in some 40% of parkinsonian patients, 6 of our 7 patients (86%) had an akinetic-rigid form of the disease. Levodopa withdrawal preceded the akinetic crisis in 4 patients: in 3 patients the akinetic crisis occurred despite adequate dopaminergic therapy, in one patient after benzodiazepine withdrawal, in another case after gastrointestinal bleeding, and in one case without known cause. Hyperthermia, tachycardia and sweating were the most common collateral manifestations. Apomorphine given subcutaneously was effective in four cases, apomorphine and amantidine were effective in one case, and one patient died during an akinetic crisis. The akinetic crisis is a distinct form of motor fluctuation in advanced stages of Parkinson's disease, with clinical signs resembling malignant neuroleptic syndrome (NMS). While NMS is related to dopaminergic receptor blockade or dopaminergic depletion, akinetic crisis can occur despite adequate dopaminergic therapy as a symptom of severe basal ganglia dysfunction related to the advanced stages of Parkinson's disease. Outcome and therapy of akinetic crisis depend on the underlying causes.
 ...
PMID:[Akinetic crisis in Parkinson disease]. 802


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>