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2

项与 Fidia Georgetown Institute for the Neurosciences 相关的药物

IDRA-5

靶点

AMPA receptor x NMDA receptor

作用机制

AMPA receptor调节剂 [+1]

在研机构-

原研机构

Fidia Georgetown Institute for the Neurosciences

在研适应症-

非在研适应症

认知障碍

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

LIGA-20

靶点-

作用机制-

在研机构-

原研机构

Fidia Georgetown Institute for the Neurosciences

在研适应症-

非在研适应症

神经系统变性病 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期-

100 项与 Fidia Georgetown Institute for the Neurosciences 相关的临床结果

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0 项与 Fidia Georgetown Institute for the Neurosciences 相关的专利（医药）

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37

项与 Fidia Georgetown Institute for the Neurosciences 相关的文献（医药）

1994-07-05·Proceedings of the National Academy of Sciences1区 · 综合性期刊

LIGA20, a lyso derivative of ganglioside GM1, given orally after cortical thrombosis reduces infarct size and associated cognition deficit.

1区 · 综合性期刊

Article

作者: Costa, E ; Polo, A ; Zivkovic, I ; Kharlamov, A ; Guidotti, A ; Armstrong, D M

A bilateral photochemically induced thrombotic lesion of rat sensorimotor cortex (approximately 3 mm in diameter and 25 mm3 in volume) is associated with a persistent cognition (learning and memory) deficit, which was evaluated with water maze tasks. The N-dichloroacetylsphingosine derivative of lysoGM1 (LIGA20) administered after the lesion either i.v. or per or reduces the infarct size by 30-40% and attenuates the associated cognition deficits, presumably by limiting the extent of damage of neurons at risk located in the surroundings of the infarcted core (i.e., area penumbra). The LIGA20 protection is dose and time dependent. Maximal protection is afforded by a single dose of LIGA20 of 34 mumol/kg i.v. 1 hr after lesion or by a dose of 270 mumol/kg per os when administered 1 hr and 24 hr after the lesion. The protective effect of LIGA20 can be observed when the drug is administered i.v. up to 6 hr after the lesion. The protective efficacy of the oral administration of LIGA20 is related to its physiochemical properties, which, unlike those of GM1, allow absorption from the gastrointestinal tract. LIGA20 given orally reaches the brain promptly and rapidly inserts into the neuronal membranes. Here, by an unknown molecular mechanism, LIGA20 selectively reduces the pathological amplification of Ca2+ signaling elicited by persistent stimulation of ionotropic glutamate receptors in the area penumbra.

1994-07-01·The Journal of pharmacology and experimental therapeutics

Mitochondrial diazepam-binding inhibitor receptor complex agonists antagonize dizocilpine amnesia: putative role for allopregnanolone.

Article

作者: Romeo, E ; Cheney, D L ; Costa, E ; Zivkovic, I ; Guidotti, A

In rats trained to retain a passive avoidance response or to retrieve a learned task in the radial and water maze tests, a pretreatment with 2-hexyl-3-indoleacetamide (FGIN-1-27) (IC50 57 mumol/kg p.o.) or 4' chlorodiazepam (4'CD) (15 mumol/kg i.p.), two steroidogenic ligands at the mitochondria diazepam-binding inhibitor receptor complex (MDRC), antagonized the performance deficit elicited by dizocilpine (0.3 mumol/kg i.p.), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. The 1-(2-chlorophenyl)-N-methyl-N-(-1-methyl-propyl)-3-isoquinoline carboxamide (PK-11195), an antagonist at MDRC in vivo, failed to modify the disruptive effect of dizocilpine in the passive avoidance response but reversed the FGIN-1-27- or 4' CD-induced antagonism of dizocilpine behavioral actions. Pretreatment with pregnenolone sulfate (48 mumol/kg i.p.), 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC) (15 mumol/kg i.v.) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) (15 mumol/kg i.v.) also reduced the passive avoidance retention deficit elicited by dizocilpine. The (17-beta)-17-[[bis(1-methylethyl)amino[carbonyl]androstane-3,5-diene-3- carboxylic acid (SKF-105111), a 5 alpha-reductase inhibitor, blocked the antagonism of dizocilpine behavioral actions by pregnenolone sulfate or by FGIN-1-27 but not those caused by THDOC or allopregnanolone either in normal or adrenalectomized-castrated rats. Thus, it is inferred that the amnesic effect of dizocilpine is counteracted by FGIN-1-27, 4'CD and pregnenolone sulfate because of their ability to increase brain accumulation of allopregnanolone.

1993-10-01·The Journal of pharmacology and experimental therapeutics

Stimulation of brain steroidogenesis by 2-aryl-indole-3-acetamide derivatives acting at the mitochondrial diazepam-binding inhibitor receptor complex.

Article

作者: Polo, A ; Costa, E ; Guidotti, A ; Romeo, E ; Korneyev, A ; Kozikowski, A P ; Cavallaro, S ; Ma, D

The 2-aryl-indole-3-acetamide derivatives, 2-hexyl-indole-3-acetamide (FGIN-1-27) and 2-hexyl-indole-3-acetamide-N-benzene-tricarboxylic acid (FGIN-1-44) displaced [3H]1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinoline-carboxamide([3H]PK 11195) and [3H]4-chlorodiazepam ([3H]4'CD) from binding sites located on the rat brain mitochondrial DBI receptor complex (MDRC) with Ki values in the nanomolar range. Both 2-aryl-indole-3-acetamide derivatives acted as agonists at the MDRC and thereby stimulated the rate of pregnenolone synthesis in isolated rat brain mitochondria; this effect was inhibited by PK 11195, an MDRC ligand that does not possess steroidogenic activity. FGIN-1-27 and FGIN-1-44 failed to bind to other transmitter receptors, including gamma-aminobutyric-A receptors. When administered orally to rats, both FGIN-1-27 and FGIN-1-44 reduced fear of novelty in the elevated plus maze test. This action was prevented by PK 11195, but not by flumazenil. FGIN-1-44, which was rapidly converted to FGIN-1-27 in the rat brain, was 3 to 4 times more potent than FGIN-1-27 in reducing fear of novelty because of its greater bioavailability. FGIN-1-27 increased the brain pregnenolone content in adrenalectomized-castrated rats pretreated with trilostane (in order to prevent metabolism of pregnenolone to progesterone). This increase was blocked by pretreatment with PK 11195. Although FGIN-1-27 and FGIN-1-44 increased the corticosterone concentration in adrenal glands and plasma of hypophysectomized rats in a PK 11195-sensitive manner, both drugs failed to increase adrenal steroidogenesis in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

100 项与 Fidia Georgetown Institute for the Neurosciences 相关的药物交易

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100 项与 Fidia Georgetown Institute for the Neurosciences 相关的转化医学

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