Source:http://linkedlifedata.com/resource/pubmed/id/10700601
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2000-4-25
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| pubmed:abstractText |
R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino) ethoxy]ethanol hydrochloride (T-588) enhances acetylcholine release from the frontal cortex and hippocampus in rats, and can ameliorate cognitive dysfunction in various amnesia models of rodents. T-588 protects rat cerebellar granule cells from glutamate neurotoxicity in culture. This agent also inhibits facilitation in the crayfish neuromuscular junction and mammalian cerebellum. Clinical trials of T-588 are underway in patients with Alzheimer's disease. We attempted to determine whether T-588 treatment ameliorates neuromuscular dysfunction in the wobbler mouse, an animal model of motoneuron disease (MND). After the initial diagnosis of MND at the age of 3-4 weeks, wobbler mice were orally administered T-588 (3, 10, 30 mg/kg) or vehicle daily for 4 weeks in a blinded fashion. We compared symptomatic, pathological and biochemical changes among the groups. In comparison with vehicle, T-588 administration potentiated grip strength, attenuated forelimb contracture and increased the weight of the biceps muscles. T-588-treated mice had retarded denervation muscle atrophy and elevated activities of choline acetyltransferase (ChAT) or lactate dehydrogenase in the biceps muscles. T-588 treatment also enhanced ChAT activities and promoted formation of cyclic adenosine monophosphate in the cervical cord. Pharmacokinetic study also showed that T-588 was transported efficiently into the cerebrum and spinal cord following oral administration. Thus, T-588 treatment delayed the progression of wobbler murine MND. Our findings suggest that this agent has therapeutic potential in human motor neuropathy or MND.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Stimulants,
http://linkedlifedata.com/resource/pubmed/chemical/Choline O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Diethylamines,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/T 588,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0006-8993
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
6
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| pubmed:volume |
858
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
84-91
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10700601-Administration, Oral,
pubmed-meshheading:10700601-Animals,
pubmed-meshheading:10700601-Cell Count,
pubmed-meshheading:10700601-Cells, Cultured,
pubmed-meshheading:10700601-Central Nervous System Stimulants,
pubmed-meshheading:10700601-Choline O-Acetyltransferase,
pubmed-meshheading:10700601-Cyclic AMP,
pubmed-meshheading:10700601-Diethylamines,
pubmed-meshheading:10700601-Disease Models, Animal,
pubmed-meshheading:10700601-Disease Progression,
pubmed-meshheading:10700601-Drug Evaluation, Preclinical,
pubmed-meshheading:10700601-Forelimb,
pubmed-meshheading:10700601-Hand Strength,
pubmed-meshheading:10700601-L-Lactate Dehydrogenase,
pubmed-meshheading:10700601-Mice,
pubmed-meshheading:10700601-Mice, Inbred C57BL,
pubmed-meshheading:10700601-Mice, Neurologic Mutants,
pubmed-meshheading:10700601-Motor Neuron Disease,
pubmed-meshheading:10700601-Muscle, Skeletal,
pubmed-meshheading:10700601-Organ Size,
pubmed-meshheading:10700601-Spinal Cord,
pubmed-meshheading:10700601-Thiophenes
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| pubmed:year |
2000
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| pubmed:articleTitle |
T-588, a novel neuroprotective agent, delays progression of neuromuscular dysfunction in wobbler mouse motoneuron disease.
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| pubmed:affiliation |
Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6, Ohashi, Meguro-ku, Tokyo, Japan.
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| pubmed:publicationType |
Journal Article
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