Basic Research of the senile dementia: Cerebro-protective glutamate antagonists.
| Project/Area Number |
62570100
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SHINOZAKI H. The Tokyo Metropolitan Institute of Medical Science, 薬理, 研究員 (20109945)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA M. The Tokyo Metropolitan Institute of Medical Science, 薬理, 研究員 (90124437)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Glutamate / Glutamate blocker / Excitatory amino acids / 老人性痴呆 / スチゾロビン酸 / キスカル酸 |
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| Research Abstract |
Acromelic acid, one of the kainoids that possess a constitutional moiety of kainic acid, has been proven to be one of the most potent agonists of excitatory amino acids in both vertebrates and invertebrates. Acromelic acid is superior to other kainoids in depolarzing activity of the rat spinal motoneuron. The most pronouced behavioural changes after the systemic injection of kainic acid are strong immobility, increased incidence of wet-dog-shake, long-lasting generalized tonic-clonic convulsions and brain damages. On the other hand, acromelic acid caused a marked long-lasting tonic extension of the hindimb, which was followed by a flaccid paralysis of skeletal muscles of the hindlimb. This is quite different from the kainate-induced symptom. Most rats receiving acromelic acid at an intravenous dose of 5 mg/kg died from tonic convulsions within about 1 hour, but some surviving rats on the next day of the injection demonstrated severe tonic extension of the hindlimb with tremor and a medially curved rigid tail, which was significantly reinforced by sensory stimuli. These symptoms lasted for more than 2 months without any further administration of acromelic acid. Pathological observations demonstrated swellings of the motoneuron and the glyosis in the Dorsal horn. This is a nice model for neuron damage in the mammalian central nervous system. In additon, actions of some conformationally restricted analogues of glutamte, isomers of L- -(carboxycyclopropyl)glycine (L-CCG) were investigated in the newborn rat spinal cord motoneuron. Of these, the (2R,3S,4S)ismoers of d-CCG was the most markedly powerful, its depolarizing activity being about 5 times more potent than NMDA in the isolated rat spinal cord. These compounds are expected to be nice tools for elucidating the mechanism underlying neurone damage in senile dementia.
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Report
(3 results)
Research Products
(22 results)
