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 purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.
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PMID:Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism. 191 2

After local surgical exposure, we administrated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) directly into the right common carotid artery of 5 rhesus monkeys. All the monkeys manifested akinesia, rigidity and postural tremor of the contralateral limbs, and spontaneous circling toward the MPTP treated side. These disturbances began to appear 3-4 days after injection, peaking at one month, and continued until the day of sacrifice. After treatment with madopar and apomorphine, marked improvements of the motor impairments appeared and a striking reversal of the direction of rotation away from the MPTP-treated side occurred in a dose-dependent manner. The ipsilateral neurotoxicity was confirmed biochemically by 99% reduction in the caudate-putamen dopamine levels and histologically by selective cell loss in the substantia nigra of the MPTP-treated side. It is concluded that this primate model of hemiparkinsonism is easy to reproduce and life is maintained with good health otherwise. So it may be more feasible for behavioral and pharmacological studies of Parkinson's disease.
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PMID:Hemiparkinsonism in monkeys following unilateral common carotid artery infusion of MPTP. A study of behavior, biochemistry and histology. 193 58

Parkinson's disease (PD) is a common neurodegenerative disease of old age characterized by triad of akinesia, rigidity and tremor, reduction of dopamine (DA) content in the nigrostriatum, and severe degeneration of neuron in the substantia nigra. The significant changes after the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rhesus monkeys and C57 black mice are (a) serotonin-like reactions and Parkinsonian symptoms in monkeys and "stickclimbing" disturbance in mice; (b) marked DA reduction in substantia nigra (72.5%), putamen (93.3%), caudate nucleus (91.2%) of monkeys and striatum (94%) of mice; (c) reduction of Met-enkephalin (75%) and Leu-enkephalin (66%) in mouse striatum; and (d) severe degeneration of neurons in the substantia nigra of monkeys and mice. The results suggest that MPTP-treated monkey and C57 black mouse provides useful Parkinsonian animal models and produces behavioral, biochemical and histopathological changes similar to those of human PD.
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PMID:[Experimental research on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian animal models in the rhesus monkey and C57 black mouse]. 216 92

The selective dopaminergic antagonist ligands [3H]SCH 23390 and [3H]sulpiride were used to reveal autoradiographically dopamine D1 and D2 receptors, respectively, in brain sections from monkeys which had received unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing loss of dopamine-containing neurones of the substantia nigra pars compacta. The monkeys developed hemi-parkinsonian symptoms (tremor, bradykinesia) in limbs contralateral to the side of the toxin infusion. Administration of apomorphine (0.05-0.25 mg/kg) caused contralateral rotational behaviour, and reversal of the parkinsonian symptoms. Loss of forebrain dopaminergic terminals was assessed autoradiographically using [3H]mazindol to label dopamine uptake sites. A reduction in these sites of 97% (mean brain value) in the caudate nucleus, and 91% in the putamen, as compared with binding values from untreated control monkeys, was accompanied by a significant increase in the binding of [3H]sulpiride (D2) in these structures. In contrast, in the same animals there was no similar increase in [3H]SCH 23390 binding to D1 receptors in the denervated areas. These results suggest that in the parkinsonian brain, where the dopaminergic innervation of the caudate nucleus and putamen has been lost, D2 receptors may be more susceptible than D1 receptors to changes, revealed here as an increase in [3H]sulpiride binding sites.
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PMID:Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis). 219 72

Quantitative 2-[14C]deoxyglucose autoradiography was used to map the pattern of alterations in local cerebral glucose utilization associated with unilateral lesions of the substantia nigra pars compacta produced by the infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into one internal carotid artery of rhesus monkeys. These monkeys become hemiparkinsonian, displaying rigidity, bradykinesia, and tremor of the limbs contralateral to the side of MPTP infusion; during spontaneous activity they turn toward the side of the lesion. Eighty-two brain areas were examined, and statistically significant metabolic changes were confined mainly to basal ganglia structures ipsilateral to the side of the lesion. Glucose utilization was reduced in the substantia nigra pars compacta and ventral tegmental area, i.e., in the areas of cell loss. Increases in glucose utilization in regions normally innervated by the lesioned area were observed in the post-commissural portions of the putamen and dorsolateral caudate. Other structures showing statistically significant metabolic changes were the external segment of the globus pallidus (+40%), subthalamic nucleus (-17%), and pedunculopontine nucleus (+15%). There were also smaller changes in portions of the thalamus (ventral anterior nucleus, parafascicular nucleus) and premotor cortex. All significant metabolic changes were confined to the side of the substantia nigra lesion and were essentially restricted to regions involved in the production of movement or maintenance of posture.
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PMID:Local cerebral glucose utilization in monkeys with hemiparkinsonism induced by intracarotid infusion of the neurotoxin MPTP. 231 6

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.
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PMID:Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. 240 38

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

1. We quantitatively assessed deficits in the initiation and execution of arm movements occurring after destruction of nigrostriatal dopamine neurons by systemic administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Sigma). Three monkeys performed a reaction time task in which they reached toward a single and constant target for food reward. 2. After administration of MPTP, all three monkeys showed hypokinesia necessitating dopamine precursor or receptor agonist treatment. The partial recovery of one animal from initial akinesia after 19 days permitted discontinuation of dopaminergic drug therapy, although marked hypokinesia remained present. The two other animals displayed additional, intermittent phases of rigidity and activation tremor and needed continuous dopaminergic drug therapy for most of the postlesion period. 3. Administration of MPTP significantly prolonged EMG reaction time in prime mover muscles and arm movement reaction time by 47-225% and 18-129%, respectively, on the six sides of the three animals, compared with control measurements before the lesion. EMG and arm movement reaction time increased over consecutive trials in most sessions comprising 110-130 movements, the first 20 movements showing almost normal values. The delay time between onsets of EMG and arm movement showed unsystematic changes. These deficits in movement initiation were observed both with and without dopamine precursor therapy. They lasted during the whole testing period of several months. 4. Linear correlations between arm movement onset and EMG onset in the two prime mover muscles, the extensor digitorum communis and the biceps, showed coefficients of mostly 0.7-0.9, both before and after MPTP. These data suggest that the temporal relationship between onsets of arm movement and EMG were not substantially affected by MPTP. 5. Arm movement time was divided into two phases. The duration of movement between the resting key and the target, a small food-containing box located ahead of the animal, was denoted as reaching movement time. The following hand manipulation inside the food box was measured as box movement time. After MPTP, both measures were significantly prolonged by 10-103% and 12-251%, respectively, on the six sides of the three monkeys. These deficits in movement execution were observed both with and without dopaminergic drug therapy and during the whole testing period. 6. Task performance after MPTP treatment was studied in one monkey in the absence of dopaminergic drug therapy. EMG and arm movement reaction times recovered partially over several weeks, while the prolongations in reaching and box movement times remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Deficits in reaction times and movement times as correlates of hypokinesia in monkeys with MPTP-induced striatal dopamine depletion. 278 68

Extracellular single unit activity was recorded from neurons of the internal (GPi) and external (GPe) pallidal segments, and from 'border cells' (Bor) which are part of the nucleus basalis, in 2 cynomolgus monkeys rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Cell counts showed that at least 90% of the nigral neurons of the compacta-type were degenerated. Electrical stimulation was applied to 3 sites bilaterally in the striatum: one in the caudate nucleus and 2 in the putamen. The results were compared to those obtained in intact monkeys. In the parkinsonians, more neurons of the 3 types responded to ipsilateral stimulation. The difference was even greater for contralateral responses, except in the case of Bor neurons. Greater proportions of the 3 types of neurons also responded to 2 and 3 sites and showed convergent responses to both the caudate nucleus and the putamen. The magnitude of the responses was larger. These results are in accordance with the excessive and unselective responses of the same neurons to passive limb movement, obtained in the same animals and described previously. The electrical stimulation allowed more detailed analyses of the responses. The major change in the responses of GPi and Bor neurons was the more frequent and larger late inhibitions, whereas the excitations were larger in GPe neurons. Long lasting oscillatory responses occurred frequently in the parkinsonians, mainly in GPi, and at frequencies close to the tremor displayed by the animals. Responses beginning with early inhibition were displayed by neurons located in the center of the pallidal zone of influence of each striatal stimulation site, as in intact animals, but in the GPi of the parkinsonians they were less frequently curtailed by excitation. Moreover, in the parkinsonians, the zones of influence were larger in both GPi and GPe, mainly because of the expansion of their periphery, where responses began with excitation and had lower thresholds than in intact animals. The dopamine agonist apomorphine normalized the responses in the parkinsonians. Thus, both the temporal and spatial magnitudes of inhibitions and excitations are abnormal at the output of the basal ganglia in parkinsonism.
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PMID:Responses of pallidal neurons to striatal stimulation in monkeys with MPTP-induced parkinsonism. 279 Apr 69

Six monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine developed a Parkinsonian syndrome (rigidity, akinesia, flexed posture and tremor). In both high and low dose groups, neurons in the substantia nigra were selectively damaged. At high dose levels, nigral neurons were severely damaged, but because the monkeys died, the evolution of the pathology could not be studied. At low dose levels, some nigral neurons survived, and a significant number of these nerve cells showed reductions in the immunoreactivity of tyrosine hydroxylase. Axonal pathology was conspicuous in the nigrostriatal pathway. Loss of the immunoreactivity of tyrosine hydroxylase in perikarya may represent a retrograde axonal reaction, a potentially reversible response. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model should prove useful for investigating abnormalities occurring as a consequence of dysfunction of the nigrostriatal system, for examining processes associated with repair of damaged neuronal systems, and for developing and testing therapeutic approaches designed to prevent or ameliorate the Parkinsonian syndrome.
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PMID:Injury of nigral neurons exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: a tyrosine hydroxylase immunocytochemical study in monkey. 287 15


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