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 antitremor effect of the D2 agonist LY 171555 and of the D1 agonist CY 208-243 alone and in combination was tested in a monkey previously rendered parkinsonian by MPTP and displaying exceptionally a rest tremor in the limbs. The D2 agonist suppressed rest tremor in a dose-dependent fashion. The D1 agonist by itself had no effect but it potentiated the effect of a small dose of LY 171555.
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PMID:Effect of LY 171555 and CY 208-243 on tremor suppression in the MPTP monkey model of parkinsonism. 134 51

Following the demonstration of an anti-tremor effect of ethosuximide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model, we have tested the effect of this drug in 10 patients with typical parkinsonian tremor. Six patients suffered from Parkinson's disease with prominent, relatively drug-resistant rest tremor. The other four patients had a drug-induced parkinsonian tremor due to neuroleptic agents taken for a psychiatric condition. Five of the six parkinsonian patients and three of the four psychiatric patients reported within a few days a marked and intolerable exacerbation of their tremor. One patient in each group was improved, and this improvement was verified in repeated examinations. Thus, for unknown reasons, the effect of ethosuximide was not as predicted by the monkey model. Among possible explanations is the fact that we had chosen patients with drug-resistant tremor.
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PMID:Ethosuximide and tremor in Parkinson's disease: a pilot study. 135 60

Based on the hypothesis that low-threshold calcium conductance in the thalamus might be involved in the pathophysiology of parkinsonian tremor, ethosuximide was given chronically to a monkey previously treated with MPTP and displaying exceptionally a typical rest tremor. After 5 days of daily treatment, the tremor was reduced by 60%. Diltiazem and verapamil which act on different calcium channels had no such effect. Ethosuximide also potentiated the anti-tremor effect of the dopamine D2 agonist LY-171555.
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PMID:Effect of ethosuximide on rest tremor in the MPTP monkey model. 135 61

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

The effect of intranasal substance P injection on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in caudate nuclei (CN) was investigated. MPTP or reserpine administration in old rats induced oligokinesia, rigidity and tremor followed by the high amplitude slow and rapid waves in both CN. The bilateral intranasal injection of substance P (25 micrograms/kg) resulted in an increase in motor activity and almost completely abolished the rigidity and tremor. The reduction of extrapyramidal symptoms was considered as a result of the inhibition of GPEE in CN. The possibility of substance P entry from nasal cavity into the brain was discussed. The changes of the substance P balance in nigrostriatal system was suggested to be on of the pathogenetic links of parkinsonian syndrome.
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PMID:[Effects of intranasally administered substance P in parkinsonian syndrome]. 138 92

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.
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PMID:Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys. 138 70

Peak dose dyskinesia is a major problem in the treatment of parkinsonian patients with levodopa and yet this remains the best pharmacological agent for treating the condition. The hypothesis which this research set out to test was that thalamotomy in the area of the thalamus which receives the input from the medial segment of the globus pallidus would decrease or prevent the dyskinesia. A well established primate model of parkinsonism was used. Eight monkeys (Macaca fascicularis) were rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Regular dosing with levodopa or apomorphine reliably resulted in peak dose dyskinesia. Thalamotomy was carried out using a radiofrequency electrode. To ensure that the appropriate area of the thalamus was targeted, that is the area receiving the pallidal input, an anatomical tracing study was carried out. The anterograde anatomical tracer horseradish peroxidase, covalently bound to wheatgerm agglutinin, was injected into the medial segment of the globus pallidus bilaterally in three monkeys. The target site for thalamotomy was accurately worked out from the tracings obtained. Chorea was usually abolished and always reduced by a thalamotomy in the pallidal terminal territory. This result was obtained after 10 thalamotomies: 4 animals receiving bilateral lesions, with an interval between operations, and 2 animals undergoing unilateral surgery. Lesions in three control sites were carried out and had no permanent effect on chorea. The effect of lesions in other areas was also assessed. Dystonia was not relieved by any thalamic lesion. Thalamotomy is a long established procedure used to help parkinsonian tremor. Appropriately placed thalamotomy should be considered for the relief of disabling peak dose dyskinesia, which is predominantly choreic, in parkinsonian patients on otherwise successful levodopa therapy.
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PMID:The use of thalamotomy in the treatment of levodopa-induced dyskinesia. 158 Jan 97

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 study attempted to verify whether activation of locus coeruleus neurons by alpha 2 antagonists might improve parkinsonian signs. Treatment with the racemic alpha 2 antagonist R 47 243 of a monkey with MPTP-induced parkinsonian signs normalized blink rate, reduced resting tremor, and improved several other parkinsonian signs. In a second experiment, the (-)-isomer R 62 651 produced a gradual change in tremor which was the inverse of the mannner in which tremor had become installed as the result of progression earlier upon the MPTP challenge. It is proposed that further research be conducted to determine whether alpha 2 antagonists may beneficially influence the progression of Parkinson's disease.
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PMID:Effects of an alpha 2 antagonist in a 20-year-old Java monkey with MPTP-induced parkinsonian signs. 167 7

Cynomolgus monkeys received intracarotid injections of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5-mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.
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PMID:Intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration: biochemical and behavioral observations in a primate model of hemiparkinsonism. 169 Feb 67


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