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 effects of anticholinergic and dopaminergic drugs used for Parkinson's disease were studied on the tremor induced by physostigmine (0.3-3.0 mg/kg) in rats. For the measurement of tremor a new electronic device was employed. Atropine (0.3-1.2 mg/kg) and biperiden (0.01-1.0 mg/kg) reduced the physostigmine-induced tremor in a dose-related manner and could abolish it. Biperiden was less potent than atropine. Methylatropine in a dose of 1.2 mg/kg slightly inhibited the tremor. Amantadine (0.3-3.0 mg/kg) reduced the tremor but only to a certain degree. Bromocriptine (0.1-10.0 mg/kg) reduced it in a manner that was not dose-related. Pimozide potentiated the tremor in the dose of 0.2 mg/kg but not in larger doses. At the onset of the tremor, a small decrease in rectal temperature occurred. The hypothermia lasted significantly longer than the tremor. Neither the anticholinergic nor the dopaminergic anti-Parkinson drugs altered the hypothermic effect of physostigmine. The results show that those anti-Parkinson drugs, which act by increasing the dopaminergic activity can counteract the tremor induced by physostigmine. However, these drugs are clearly less active than th anticholinergic anti-Parkinson drugs.
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PMID:Drugs for Parkinson's disease reduce tremor induced by physostigmine. 662 15

The human gene that codes for the protein alpha-synuclein has been transferred into the Drosophila melanogaster genome. The transgenic flies recapitulate some of the essential features of Parkinson's disease. These include the degeneration of certain dopaminergic neurons in the brain accompanied by the appearance of age-dependent abnormalities in locomotor activity. In the present study, we tested the locomotor response of these transgenic flies to prototypes of the major classes of drugs currently used to treat this disorder. A time course study was first conducted to determine when impaired locomotor activity appeared relative to normal "wild-type" flies. A climbing or negative geotaxis assay measuring the ability of the organisms to climb up the walls of a plastic vial was used. Based on the results obtained, normal and transgenic flies were treated with each of the drugs in their food for 13 days and then assayed. The activity of transgenic flies treated with L-DOPA was restored to normal. Similarly, the dopamine agonists pergolide, bromocriptine, and 2,3,4,5-tetrahydro-7,8-dihydroxy- 1-phenyl-1H-3-benzazepine (SK&F 38393) were substantially effective. Atropine, the prototypical muscarinic cholinergic receptor antagonist, was also effective but to a lesser extent than the other antiparkinson compounds. p-Chlorophenylalanine, an inhibitor of serotonin synthesis, was without beneficial effect as was alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis. This behavioral study further demonstrates the utility of this model in studying Parkinson's disease and reinforces the concept that inhibition of the action of alpha-synuclein may be useful in its treatment as may dopamine D(1) receptor agonists.
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PMID:Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster. 1175 2

The cerebral cortex and basal ganglia (BG) form a neural circuit that is disrupted in disorders such as Parkinson's disease. We found that neuronal activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave electroencephalography but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine [N-methyl-d-aspartate (NMDA) receptor antagonist] and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist). Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN) input to internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr), while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu) dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe), and STN but increased activity of the GPi, SNr, and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders.
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PMID:Neuronal activity (c-Fos) delineating interactions of the cerebral cortex and basal ganglia. 2472 55