SGS-742(SGS-742) - 药物靶点：GABAB receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [2]

靶点

GABAB receptor

作用机制

GABAB receptor拮抗剂(γ-氨基丁酸B受体拮抗剂)

治疗领域

神经系统疾病遗传病与畸形内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

阿尔茨海默症癫痫发作琥珀酸半醛脱氢酶缺乏症

原研机构

Saegis Pharmaceuticals, Inc.

在研机构-

非在研机构

National Institute of Neurological Disorders & Stroke

Saegis Pharmaceuticals, Inc.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C7H18NO2P

InChIKeyONNMDRQRSGKZCN-UHFFFAOYSA-N

CAS号123690-78-8

关联

2

项与 SGS-742 相关的临床试验

NCT02019667

/ Completed临床2期IIT

Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency

Objective:
To perform a clinical trial assessing the safety, tolerability and efficacy of the GABA(B) receptor antagonist SGS-742 in patients with SSADH deficiency.
Study Population:
Twenty-two children and adults with SSADH deficiency.
Design:
Double-blind, cross-over, phase II clinical trial.
Outcome Measures:
The primary outcome measures for drug efficacy will be performance on neuropsychological testing and responses to parent questionnaire. The secondary outcome measure will be TMS parameters of cortical excitation and inhibition. The outcome measures for safety will include clinical examination and neuropsychological tests.

开始日期2014-03-31

申办/合作机构

National Institute of Neurological Disorders & Stroke

NCT00093951

/ Completed临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Study of the Efficacy and Safety of SGS742 in Subjects With Mild to Moderate Alzheimer's Disease

The purpose of this trial is to determine the effect of a new drug, SGS742, on memory and cognition in patients with mild to moderate Alzheimer's disease.

开始日期2004-04-01

申办/合作机构

Saegis Pharmaceuticals, Inc.

100 项与 SGS-742 相关的临床结果

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100 项与 SGS-742 相关的转化医学

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100 项与 SGS-742 相关的专利（医药）

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84

项与 SGS-742 相关的文献（医药）

2022-07-01·The Journal of Pharmacology and Experimental Therapeutics3区 · 医学

Treatment of γ-Hydroxybutyrate Overdose with the GABAB Antagonist SGS742

3区 · 医学

Article

作者: Morris, Marilyn E ; Follman, Kristin E

High doses of the partial agonist of the GABA _B receptor, γ-hydroxybutyric acid (GHB), causes respiratory depression that can lead to death. Previously, it has been shown that GABA_B- receptor antagonism is able to prevent respiratory depression and sedation when inhibitors are pre-administered. In order to treat GHB overdoses, safety and efficacy of a treatment strategy at various times after GHB administration is necessary, in order to more closely replicate a true overdose situation. Preliminary studies developed an assay for SGS742 and determined its pharmacokinetics in rats. The effects of SGS742 on GHB-induced respiratory depression were evaluated when SGS742 administration was delayed 1 and 2 hours after intravenous or oral administration of GHB or γ-butyrolactone, a GHB prodrug. SGS742 reversed GHB-induced respiratory depression in a dose-dependent manner at both time points tested, with no effects on its toxicokinetics. However, some of the dosing paradigms resulted in toxicity in the form of tremors, seizures or abnormal movements. The tremors/seizures occurred in a manner that was dependent on both the dose and timing of SGS742 administration, and were not altered with pretreatment with gabazine, a GABA_A receptor inhibitor, and only partially reduced with pretreatment with NCS382, a selective GHB receptor antagonist. Additional studies with a second GABA_B antagonist SCH50911 demonstrated similar effects, producing reversal of respiratory depression but producing tremors and abnormal movements. Further studies are necessary in order to identify the potential use of GABA_B antagonism as a treatment strategy for GHB overdoses. Significance Statement There is no current treatment for overdoses of the drug of abuse γ-hydroxybutyric acid (GHB). Since the toxicodynamic effects of GHB, including respiratory depression and lethality, are mediated through GABA_B receptor agonism, GABA_B receptor antagonists may represent a therapeutic strategy to treat overdoses. This study demonstrates that while GABA_B receptor antagonists are effective as a pretreatment, they are less effective when administered at times after GHB administration and their administration is also associated with time- and dose-associated toxicity.

2021-11-01·Journal of Child Neurology4区 · 医学

A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

4区 · 医学

Article

作者: Zhou, Xiangping ; Schreiber, John M. ; Inati, Sara K. ; Rolinski, Rachel ; Cuento, Rose ; Wiggs, Edythe ; Theodore, William H. ; Gibson, K. Michael ; Austermuehle, Alison ; Dustin, Irene H. ; Norato, Gina ; Pearl, Phillip L.

We examined safety, tolerability, and efficacy of SGS-742, a γ-aminobutyric acid B (GABA-B) receptor antagonist, in patients with succinic semialdehyde dehydrogenase deficiency. This was a single-center randomized, double-blind crossover phase II clinical trial of SGS-742 versus placebo in patients with succinic semialdehyde dehydrogenase deficiency. Procedures included transcranial magnetic stimulation and the Adaptive Behavior Assessment Scale. Nineteen subjects were consented and enrolled; the mean age was 14.0 ± 7.5 years and 11 (58%) were female. We did not find a significant effect of SGS-742 on the Adaptive Behavior Assessment Scale score, motor threshold, and paired-pulse stimulation. The difference in recruitment curve slopes between treatment groups was 0.003 ( P = .09). There was no significant difference in incidence of adverse effects between drug and placebo arms. SGS-742 failed to produce improved cognition and normalization of cortical excitability as measured by the Adaptive Behavior Assessment Scale and transcranial magnetic stimulation. Our data do not support the current use of SGS-742 in succinic semialdehyde dehydrogenase deficiency. Trial registry number NCT02019667. Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency. https://clinicaltrials.gov/ct2/show/NCT02019667

2018-07-01·Neuropharmacology2区 · 医学

Impact on GABA systems in monogenetic developmental CNS disorders: Clues to symptomatic treatment

2区 · 医学

Review

作者: Dietmar Benke ; Hanns Möhler

Animal studies of several single-gene disorders demonstrate that reversing the molecular signaling deficits can result in substantial symptomatic improvements in function. Focusing on the ratio of excitation to inhibition as a potential pathophysiological hallmark, seven single-gene developmental CNS disorders are reviewed which are characterized by a striking dysregulation of neuronal inhibition. Deficits in inhibition and excessive inhibition are found. The examples of developmental disorders encompass Neurofibromatosis type 1, Fragile X syndrome, Rett syndrome, Dravet syndrome including autism-like behavior, NONO-mutation-induced intellectual disability, Succinic semialdehyde dehydrogenase deficiency and Congenital nystagmus due to FRMD7 mutations. The phenotype/genotype correlations observed in animal models point to potential treatment options and will continue to inspire clinical research. Three drugs are presently in clinical trials: acamprosate and ganoxolon for Fragile X syndrome and SGS-742 for SSADH deficiency. This article is part of the "Special Issue Dedicated to Norman G. Bowery".

100 项与 SGS-742 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05010

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
癫痫发作	临床2期	美国	National Institute of Neurological Disorders & Stroke	2014-03-31
琥珀酸半醛脱氢酶缺乏症	临床2期	美国	National Institute of Neurological Disorders & Stroke	2014-03-31
阿尔茨海默症	临床2期	美国	Saegis Pharmaceuticals, Inc.	2004-04-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02019667 (14-N-0033, J Child Neurol) 人工标引	临床2期	琥珀酸半醛脱氢酶缺乏症	19	SGS-742	(糧糧網窪構製鹽襯醖積) = We did not find a significant effect of SGS-742 on the Adaptive Behavior Assessment Scale score, motor threshold, and paired-pulse stimulation. 獵積願艱廠廠範壓艱築 (簾餘廠選衊簾淵衊窪齋 ) 更多	不佳	2021-05-20
				placebo
NCT02019667 (140033, CTgov)	临床2期	琥珀酸半醛脱氢酶缺乏症 \| 癫痫发作	19	Placebo (Placebo)	積獵構鏇糧鑰餘憲衊觸(構夢選夢膚鹹製憲築淵) = 醖網鏇窪選範遞鏇遞廠膚蓋襯鏇鑰範網餘範積 (製範憲繭獵鹹鬱獵餘範, 壓簾構築觸衊獵鏇廠夢 ~ 構築範膚繭蓋繭齋壓鬱) 更多	-	2020-02-24
				SGS-742 (Study Drug)	積獵構鏇糧鑰餘憲衊觸(構夢選夢膚鹹製憲築淵) = 鹹膚獵淵憲選鬱蓋鑰範膚蓋襯鏇鑰範網餘範積 (製範憲繭獵鹹鬱獵餘範, 窪齋襯積鬱製簾夢窪鏇 ~ 齋顧齋醖憲觸窪窪蓋醖) 更多