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)

Suspensions of endocrine pancreas cells were prepared by shaking collagenase-isolated rat islets of Langerhans in calcium-free buffer. When incubated with 1.0 mM substrate at pH 7.4, the cells split Pi from 5'-AMP at a rate of 87 nmol/h per microgram DNA, and from beta-glycerophosphate at a rate of 25 nmol/h per microgram DNA. Km for 5'-AMP was about 54 microM. Adenosine or theophylline inhibited the 5'-AMP hydrolysis. Homogenization of the cells increased the activity toward 5'-AMP by 23% and that toward beta-glycerophosphate by 115%. Injecting rats with cortisone had no effect on the 5'-AMP hydrolysis by whole cells but significantly increased the activity in cell homogenates; the intracellular activity toward 5'-AMP was more than doubled by the cortisone treatment. Staining whole islet cells for 5'-AMP-splitting activity resulted in a demarcation of the cell periphery in control rats. Cells from cortisone-treated rats showed heavier deposits of reaction product, and their cell periphery did not stand out as clearly. It is suggested that 5'-nucleotidase is largely an ectoenzyme in normal rat islet cells. The cells also contain an as yet unidentified intracellular phosphatase that seems to be solely responsible for the increased hydrolysis of 5'-AMP in cortisone-treated rats.
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PMID:5'-AMP hydrolysis by suspensions and homogenates of pancreatic islet cells from normal and cortisone-treated rats. 38 76

The chronic administration of theophylline was studied in twenty patients with essential tremor in a double-blind cross-over trial. The tremor was improved significantly after four weeks of treatment. In mice the chronic administration of theophylline was compared with propranolol on the modulation by adenosine, 5-HT, (-)isoprenaline or GABA of NMDA-induced depolarisation of neocortical slices. Adenosine depolarisation was abolished by two-weeks treatment with theophylline but not propranolol. Potentiation by (-)isoprenaline of NMDA responses was reduced by theophylline (100 mg/kg/day) and propranolol treatment (25 mg/kg/day), but a lower dose of propranolol further increased it. The enhancement by 5-HT of NMDA-induced depolarisation was unaffected by the pretreatment with theophylline, while the higher dose of propranolol blocked it. GABA caused no significant change of NMDA depolarisation in control slices, but after theophylline treatment (100 mg/kg/day) and propranolol administration at both doses it significantly potentiated NMDA depolarisation. The enhancement of GABA sensitivity might be an important common factor in decreasing the essential tremor after propranolol and theophylline treatment.
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PMID:The effect of theophylline on essential tremor: the possible role of GABA. 194 76

Shaking movements, similar to those made by a dog when wet, were elicited in rats by immersion in ice-water, injections of icilin, a chemical that produces sensations of cold, and naloxone-precipitated morphine withdrawal. Adenosine and 2-chloroadenosine produced dose-dependent inhibition of shaking to ice-water and icilin. The 2-chloroadenosine effect was mediated centrally because the ICV dose required to produce inhibition was not effective when given IP. Caffeine antagonized the inhibitory effects of adenosine and 2-chloroadenosine. 2-Chloroadenosine suppressed morphine-abstinence shaking as well as the body weight loss that normally accompanies withdrawal.
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PMID:Inhibition of the shake response in rats by adenosine and 2-chloroadenosine. 309 18

The continuing lack of effective long-term therapies for Parkinson's disease and other disorders in which a primary symptom is involuntary tremor is leading to a search for alternative pharmacological strategies. Adenosine is a major modulator of neuronal activity and neurotransmitter release in the central nervous system, with A1 receptors inhibiting transmitter release and A2 receptors generally enhancing release of several transmitter systems relevant to the control of movement. The A2a subtype of receptor is especially concentrated in the neostriatum and is co-localised with D2 receptors for dopamine, the affinity of which are reduced by activation of the A2a population. Antagonists of adenosine, such as theophylline, have been reported to improve the tremor in cases of Parkinson's disease and essential tremor, and the development of better and more selective A2a receptor antagonists may prove of value in these disabling disorders.
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PMID:Potential role of adenosine antagonist therapy in pathological tremor disorders. 936 77

An Adenosine Triphosphate (ATP) bioluminescence system was compared and validated against standard methods for rapid microbiological monitoring of several non-sterile pharmaceutical formulations such as creams, tablets, and capsules. Results obtained using 1%, 2.5%, and 10% of product suspensions indicated that most samples that did not contain non-microbial ATP neither inhibited the bioluminescence reaction nor did something else. Ten percent product suspensions were inoculated with different concentrations of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Candida albicans, and Aspergillus niger. Samples were incubated for 24-120 h at 35 degrees C with shaking. Results indicated a strong inhibitory effect of microbial growth, as no microorganisms were detected by using the ATP bioluminescence assay. However, when 1% and 2.5% product suspensions were spiked with the same microorganisms, positive detection was confirmed. After incubation, all microorganisms were detected by the bioluminescence system within 24-72 h. All positive samples were confirmed by using standard plating media. However, to optimize detection of all microorganisms, different enrichment media were developed.
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PMID:Adenosine triphosphate bioluminescence analysis for rapid screening of microbial contamination in non-sterile pharmaceutical samples. 1523 55

Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.
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PMID:Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. 1818 Jul 13

Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A2A antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A2A antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A2A antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A2A antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects. Adenosine A2A antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.
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PMID:Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism. 1850 58

Adenosine A(2A) receptors present in the central nervous system have been implicated in the modulation of motor functions. Accordingly, adenosine A(2A) receptor antagonists currently constitute an attractive non-dopaminergic option for use in the treatment of Parkinson's disease (PD). The highly enriched distributions of adenosine A(2A) receptors in striatopallidal neurons, and their ability to form functional heteromeric complexes with dopamine D(2) and metabotropic glutamate mGlu5 receptors, render A(2A) receptor antagonists of particular interest in the modulation of motor behavior, whilst at the same time displaying a low predisposition to inducing non-motor side effects. Furthermore, adenosine A(2A) receptor antagonists appear to exert a marked efficacy on PD tremor and in reducing the progress of underlying neurodegeneration and maladaptive neuroplasticity that complicates standard dopamine replacement treatments in PD. Finally, recent evidence has illustrated an improvement of cognitive function as well as enhancement of attention in rodents following administration of A(2A) receptor antagonists. This article is aimed at examining preclinical studies describing these findings as well as reports from clinical trials, in order to provide a comprehensive review of the evidence suggesting that this class of drugs may represent an advance in the treatment of PD.
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PMID:Adenosine A2A receptor antagonists and Parkinson's disease: state of the art and future directions. 1853 71

Adenosine A(2A) antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A(2A) antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function.
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PMID:Dopamine/adenosine interactions related to locomotion and tremor in animal models: possible relevance to parkinsonism. 1858 81

Adenosine A(1) and A(2A) receptors are colocalized with dopamine D(1) and D(2) receptors on striatal projection neurons and adenosine antagonists have been proposed as adjunctive therapies to l-DOPA treatment in Parkinson patients. We present here two studies examining the effects of selective and non-selective adenosine antagonists in two rodent models of parkinsonian tremor. Tremulous jaw movements (TJMs) were induced by either the dopamine antagonist pimozide (1.0 mg/kg) or the acetylcholine agonist tacrine (5.0 mg/kg), and were quantified by a trained observer who was blind to the treatment conditions. Animals were treated concomitantly with either caffeine (10.0 mg/kg non-selective adenosine antagonist), 8-cyclopentyltheophylline (CPT; 10.0 mg/kg; selective A(1) antagonist) or SCH58261 (8.0 mg/kg; selective A(2A) antagonist). Caffeine, CPT and SCH58261 all significantly reduced pimozide-induced TJM activity. Surprisingly administration of adenosine antagonists did not reduce tacrine-induced TJMs, and in the case of SCH58261 significantly increased TJMs compared to tacrine alone. These results indicate that antagonism at A(1) receptors may be more important for the reduction of tremor than previously supposed. Furthermore they indicate that dopamine antagonist-induced tremor models and acetylcholine agonist-induced tremor models are not entirely similar, and caution should be taken when using these models to evaluate novel therapeutics.
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PMID:Differential effects of adenosine antagonists in two models of parkinsonian tremor. 1960 22


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