Delving into the Latest Updates on SGS-742 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

GABAB receptor

Mechanism

GABAB receptor antagonists(Gamma-Aminobutyric Acid B Receptor antagonists)

Therapeutic Areas

Nervous System DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Alzheimer DiseaseSeizuresSuccinic Semialdehyde Dehydrogenase Deficiency

Originator Organization

Saegis Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

National Institute of Neurological Disorders & Stroke

Saegis Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC7H18NO2P

InChIKeyONNMDRQRSGKZCN-UHFFFAOYSA-N

CAS Registry123690-78-8

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.

Start Date31 Mar 2014

Sponsor / Collaborator

National Institute of Neurological Disorders & Stroke

NCT00093951

/ CompletedPhase 2

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.

Start Date01 Apr 2004

Sponsor / Collaborator

Saegis Pharmaceuticals, Inc.

100 Clinical Results associated with SGS-742

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100 Translational Medicine associated with SGS-742

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100 Patents (Medical) associated with SGS-742

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84

Literatures (Medical) associated with SGS-742

01 Jul 2022·The Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Treatment of γ-Hydroxybutyrate Overdose with the GABAB Antagonist SGS742

Q3 · MEDICINE

Article

Author: 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.

01 Nov 2021·Journal of Child NeurologyQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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

01 Jul 2018·NeuropharmacologyQ2 · MEDICINE

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

Q2 · MEDICINE

Review

Author: 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 Deals associated with SGS-742

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05010

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Seizures	Phase 2	US	National Institute of Neurological Disorders & Stroke	31 Mar 2014
Succinic Semialdehyde Dehydrogenase Deficiency	Phase 2	US	National Institute of Neurological Disorders & Stroke	31 Mar 2014
Alzheimer Disease	Phase 2	US	Saegis Pharmaceuticals, Inc.	01 Apr 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02019667 (14-N-0033, J Child Neurol) Manual	Phase 2	Succinic Semialdehyde Dehydrogenase Deficiency	19	SGS-742	(bhtaxzagii) = We did not find a significant effect of SGS-742 on the Adaptive Behavior Assessment Scale score, motor threshold, and paired-pulse stimulation. mcstehvlsc (wjtgxjlqqt ) View more	Negative	20 May 2021
				placebo
NCT02019667 (140033, CTgov)	Phase 2	Succinic Semialdehyde Dehydrogenase Deficiency \| Seizures	19	Placebo (Placebo)	notnktrfqz(xofxkvtvna) = ksdvjucsbb zltmemansq (ewfjkkixop, sksmzdrmgw - uqgnmpngmm) View more	-	24 Feb 2020
				SGS-742 (Study Drug)	notnktrfqz(xofxkvtvna) = xzwxujcmvb zltmemansq (ewfjkkixop, dtqdvwdnsr - vepjkphdym) View more