Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors investigated the effects of chronic intracerebroventricular (ICV) infusion of dopamine (DA) and DA agonists in animal models of DA deficiency in rodents and primates. Rats with unilateral nigrostriatal lesions induced by 6-OH-DA received infusions of DA, pergolide, lisuride, and (+)-4-propyl-9-hydroxynaphthoxacine (PHNO) for from 1 to 2 weeks through a catheter implanted into the cerebral ventricle ipsilateral to the lesion and connected to an osmotic minipump filled with the active substance. The infused animals had persistent contralateral rotation during the period of infusion. The DA infusion restored DA levels in lesioned animals. In animals treated chronically with reserpine, the ICV DA infusion restored DA levels in the brain, but akinesia was not reversed unless monoamine oxidase inhibiters were also given, intraperitoneally or ICV, with the DA infusion. An ICV infusion of PHNO reversed reserpine-induced akinesia. The infusion of DA or PHNO restored normal patterns of behavior in monkeys made akinetic by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the infusion was complicated by intolerance to the pump or frequent disconnection of the catheter. An ICV infusion of PHNO may be an alternative experimental approach to the treatment of fluctuations in patients with Parkinson's disease.
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PMID:Intracerebroventricular infusion of dopamine and its agonists in rodents and primates. An experimental approach to the treatment of Parkinson's disease. 290 93

The prevalence of overt dementia in 27 studies representing 4,336 Parkinson's disease (PD) patients was 39.9%. The studies reporting the highest incidence of intellectual impairment (69.9%) used psychologic assessment techniques, whereas studies identifying the lowest prevalence of dementia (30.2%) depended on nonstandardized clinical examinations. Neuropsychologic investigations reveal that PD patients manifest impairment in memory, visuospatial skills, and set aptitude. Language function is largely spared. Intellectual deterioration in PD correlates with age, akinesia, duration, and treatment status. Neuropathologic and neurochemical observations demonstrate that PD is a heterogeneous disorder: the classic subcortical pathology with dopamine deficiency may be complicated by atrophy of nucleus basalis and superimposed cortical cholinergic deficits, and a few patients have the histopathologic hallmarks of Alzheimer's disease. Mild intellectual loss occurs with the classic pathology, and the more severe dementia syndromes have cholinergic alterations or Alzheimer's disease. Thus, PD includes several syndromes of intellectual impairment with variable pathologic and neurochemical correlates.
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PMID:Intellectual impairment in Parkinson's disease: clinical, pathologic, and biochemical correlates. 290 99

Guided and reflex eye movements were studied in cats trained to make orienting saccades toward visual and auditory targets. Injections of a GABA-agonist (Muscimol) or GABA-antagonists (Bicuculline and Picrotoxin) were made in the Substantia Nigra pars reticulata (SNpr). Bicuculline and Picrotoxin, whether unilaterally or bilaterally injected had no effect on the posture nor the oculomotor performance of the animals. Neck muscle activity remained symmetrical. Unilateral injections of Muscimol produced oro-facial akinesia, reduction of the number of eye movements, contralateral head turning, visual neglect mostly (but not only) for ipsilateral visual space. Balance between the gains of the vestibulo-ocular reflex (VOR) in the two directions of movement was changed. Gain was decreased for the ipsilateral rotation. The optokinetic nystagmus (OKN) was not affected. Contralateral neck muscles were hypertonic. After bilateral injections of Muscimol, the cats did not orient. The VOR was normal when the injections induced no postural asymmetry. Hypertony was bilateral. Implications of these results for the role of the basal ganglia in motor control are discussed. We suggest that in Parkinson's disease the fixed inhibitory drive of the SNpr on the tectum and on the thalamus is disrupted.
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PMID:Role of the cat substantia nigra pars reticulata in eye and head movements. II. Effects of local pharmacological injections. 298 33

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

A 60-year-old man who had Parkinson's disease for 25 years became unable to maintain the upright position of the trunk while standing or walking. Because of a loss of postural fixation, his trunk sank forward until his back was horizontal. Fifteen years before, a bifocal implantation of radioactive yttrium-90 had been performed by a stereotaxic procedure at the level of the globus pallidus (GP) and the ventrolateral thalamus, respectively on the right side. A second operation, 2 years later, had been made by electrocoagulation in the left ventrolateral thalamus. Postmortem examination showed the following features (a) neuronal cell loss in the pigmented nuclei of the brainstem with intracellular Lewy bodies and gliosis. These data corresponded with the usual pathology of idiopathic Parkinson's disease; (b) surgical lesions resulting from the previous stereotaxic operations in the right GP and the ventrolateral thalamus on both sides and (c) neuronal cell loss without gliosis in the right GP that was evident in regions spared by the surgical lesion. Moreover, these degenerative changes were particularly seen in the left GP, which was surgically unlesioned. The ansa lenticularis was demyelinated on both sides. These data might be consistent with a retrograde degenerative process affecting the pallidothalamic projections. Beside the role of the neuronal cell loss affecting the pars compacta of the substantia nigra (SN) in akinesia, the role of the lesions affecting the G.P. in the genesis of postural disorders is suggested.
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PMID:Long-term follow-up after stereotaxic basal ganglia surgery in parkinsonism. A neuroanatomical study of a case showing unusual postural disorders. 306 40

L-Threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was administered as a means of treating akinesia in 9 patients with Parkinson's disease and one with pure akinesia. Akinetic symptoms were improved in 7 of 10 patients. During chronic L-threo-DOPS treatment, cerebrospinal fluid (CSF) and plasma concentrations of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and L-threo-DOPS were measured in these 10 patients. The results show that there were no significant changes in either CSF or plasma free MHPG concentrations before or during L-threo-DOPS administration. The L-threo-DOPS concentration during treatment was not measurable in the CSF of 2 patients nor in the plasma of 1 out of 4 patients given only L-threo-DOPS. It was, however, measured in all patients treated with a combination of L-threo-DOPS and L-DOPA plus carbidopa. The results show that L-threo-DOPS is transported into the CSF, and suggest that its active mechanism may be further clarified by studying its action on not only noradrenaline, but also other neurotransmitters.
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PMID:Effect of L-threo-3,4-dihydroxyphenylserine chronic administration on cerebrospinal fluid and plasma free 3-methoxy-4-hydroxy-phenylglycol concentration in patients with Parkinson's disease. 308 14

Two main forms of declining motor performance are evident in Parkinson's disease: response fluctuations and "loss of benefit", i.e., the progression of the disease without "on-off" symptoms. (-)Deprenyl has a favourable beneficial effect in reducing the mild forms of response fluctuations. The addition of (-)deprenyl in such patients to the continuing substitution therapy prevents the development of more severe "on-off" manifestations. In severely disabled patients with irregular response swings or permanent akinesia the use of (-)deprenyl as an adjuvant drug cannot modify anymore the course of the disease.
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PMID:(-)Deprenyl in the treatment of decompensated Parkinson's disease. 309 59

Selegiline is a useful adjuvant drug in the treatment of Parkinson's disease. In the early phase selegiline can be given in monotherapy. Its effect is not always sufficient to eliminate all the symptoms. In spite of this observation the administering of selegiline as monotherapy can be useful because in case of the immediate introduction of levodopa therapy untoward effects may appear in an early stage of treatment. In the course of substitution therapy selegiline successfully replaces about 30% of levodopa administered in "de novo" parkinsonian patients. Selegiline has a favourable beneficial effect in reducing the mild forms of response fluctuations. The addition of selegiline in such patients to the continuing substitution therapy prevents the development of more severe "on-off" manifestations. In severely disabled patients with irregular response swings or permanent akinesia the use of selegiline as an adjuvant drug cannot modify anymore the course of the disease.
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PMID:Selegiline in the early and late phases of Parkinson's disease. 312 97

28 patients with Parkinson's disease and long-term levodopa therapy have received additional selegiline (10 mg/d) over the past 3 years and been followed up for a mean period of 18.8 months. Two thirds improved with a reduction of global disability and amelioration of end-of-dose effects, nocturnal and early-morning akinesia. Peak-dose dyskinesias tended to increase with selegiline while biphase and off-period involuntary movements improved in some cases. Patients already on maximally tolerated doses of levodopa and those with severe on-off swings did not gain significant benefit. 8 of 18 responders lost their initial response within 1.5 years.
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PMID:Experience with selegiline in the treatment of Parkinson's disease. 312 99

In two trials, we have studied the effectiveness and tolerability of L-deprenyl, a selective MAO B inhibitor, in the treatment of end of dose akinesia in patients with Parkinson's disease. The first trial was designed as an open controlled trial. In the L-deprenyl phase, an improvement in fluctuations in motor function as well as an overall reduction in the sum score of Webster's rating scale from 12.5 to 8.9 was observed, which almost returned to baseline during the placebo phase. The second trial was designed as a randomized trial comparing L-deprenyl therapy with a low-dose bromocriptine regimen. Both therapeutic approaches yielded the same results with respect to fluctuations; the CURS sum score dropped from 37 to 26. As regards tolerability, however, L-deprenyl was superior to bromocriptine.
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PMID:R-(-)-deprenyl in the treatment of end-of-dose akinesia. 312 3


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