Abstract：
:The GABA(B) receptor antagonist SGS742 (CGP36742) displays pronounced cognition enhancing effects in mice, young and old rats and in Rhesus monkeys in active and passive avoidance paradigms, in an eight-arm radial maze and a Morris water maze and in a social learning task. SGS742 blocks the late inhibitory postsynaptic potential and the paired-pulse inhibition of population spikes recorded from CA1 pyramidal neurons of the hippocampus of rats in vitro and in vivo. SGS742 significantly enhances the release of glutamate, aspartate, glycine and somatostatin in vivo. Chronic administration of SGS742 causes an up-regulation of GABA(B) receptors in the frontal cortex of rats. Single doses cause a significant enhancement of the mRNA and protein levels of NGF and BDNF in the cortex and hippocampus of rats. The observed antidepressant effects of SGS742 in rats may be explained by these findings. SGS742 was well tolerated in experimental animals as well as in young and elderly human volunteers with an absolute bioavailability in humans of 44%. In a Phase II double-blind, placebo-controlled study in 110 patients with mild cognitive impairment (MCI), oral administration of SGS742 at a dose of 600 mg t.i.d. for 8 weeks significantly improved attention, in particular choice reaction time and visual information processing as well as working memory measured as pattern recognition speed. A second Phase II clinical trial in 280 Alzheimer's disease patients is underway.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Froestl W,Gallagher M,Jenkins H,Madrid A,Melcher T,Teichman S,Mondadori CG,Pearlman Rdoi
10.1016/j.bcp.2004.07.030subject
Has Abstractpub_date
2004-10-15 00:00:00pages
1479-87issue
8eissn
0006-2952issn
1873-2968pii
S0006-2952(04)00544-1journal_volume
68pub_type
临床试验,杂志文章,随机对照试验abstract：:Casein-elicited rat peritoneal polymorphonuclear leukocytes (PMNL) and rabbit platelets were prelabelled with [1-14C]arachidonic acid, and the effect of timegadine, a new anti-inflammatory agent, on the release and metabolism of arachidonic acid induced by A23187 (PMNL) and thrombin (platelets) was studied and compare...
journal_title：Biochemical pharmacology
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更新日期：1982-08-15 00:00:00
abstract：:The role of nitric oxide (NO)/guanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway in the regulation of fatty acid metabolism was investigated in rat hepatocytes. Treatment with NO donors, which are known to activate soluble guanylyl cyclase, inhibited in parallel fatty acid synthesis de novo and acetyl-CoA c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01623-4
更新日期：2003-03-01 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：2006-05-14 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2016-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2000-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2016-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90153-8
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.05.025
更新日期：2019-08-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90750-6
更新日期：1985-03-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90264-x
更新日期：1994-06-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(93)90147-o
更新日期：1993-02-09 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bcp.2018.08.020
更新日期：2018-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01351-5
更新日期：2002-11-01 00:00:00
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更新日期：2009-10-15 00:00:00
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1998-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2002-07-01 00:00:00
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更新日期：2002-06-01 00:00:00
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pub_type： 杂志文章
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更新日期：1992-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90423-g
更新日期：1992-08-18 00:00:00
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pub_type： 杂志文章
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更新日期：1998-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,收录出版
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更新日期：2010-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.08.020
更新日期：2016-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.11.021
更新日期：2008-03-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90644-7
更新日期：1987-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90456-4
更新日期：1987-11-15 00:00:00
