Details
Stereochemistry | ACHIRAL |
Molecular Formula | C7H18NO2P |
Molecular Weight | 179.1971 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCP(O)(=O)CCCN
InChI
InChIKey=ONNMDRQRSGKZCN-UHFFFAOYSA-N
InChI=1S/C7H18NO2P/c1-2-3-6-11(9,10)7-4-5-8/h2-8H2,1H3,(H,9,10)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15451390Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8216160 | https://www.ncbi.nlm.nih.gov/pubmed/7650685 | https://www.ncbi.nlm.nih.gov/pubmed/18984654
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15451390
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8216160 | https://www.ncbi.nlm.nih.gov/pubmed/7650685 | https://www.ncbi.nlm.nih.gov/pubmed/18984654
CGP-36742 (3-Aminopropyl-n-butyl-phosphinic acid) is one of the first GABAB receptor antagonists that can penetrate the blood-brain barrier after peripheral administration. Although its affinity for GABA B binding sites labeled with a tritiated agonist is modest, being in the low micromolar range, it displays significant pharmacological activity when administered either orally or parenterally. CGP 36742 was effective in the learned helplessness paradigm in rats, dose-dependently improving the escape failures induced by the inescapable shocks, suggesting that it may have an antidepressant profile. CGP36742 displays pronounced cognition enhancing effects 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. CGP36742 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. CGP36742 significantly enhances the release of glutamate, aspartate, glycine and somatostatin in vivo. Chronic administration of CGP36742 causes an up-regulation of GABA(B) receptors in the frontal cortex of rats. The effects of CGP36742 on cognition were investigated in a double-blind, placebo-controlled study undertaken as the first assessment of the efficacy of CGP36742 in 110 patients age 59–85 years with Mild cognitive impairment. The results showed significant improvement in working memory, psychomotor speed and attention with SGS742 as compared with placebo. SGS742 appeared to be safe and well tolerated in this study.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2753 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7650685 |
38.0 µM [IC50] | ||
Target ID: CHEMBL3561 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18528996 |
62.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
48 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg 3 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
15.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
27.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
262 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
252 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg 3 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
136 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
208 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
385 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg 3 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
2.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8739022 |
600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
SGS-742 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
The actions of orally active GABAB receptor antagonists on GABAergic transmission in vivo and in vitro. | 1993 Mar 23 |
|
AMPA and GABA(B) receptor antagonists and their interaction in rats with a genetic form of absence epilepsy. | 2001 Nov 2 |
|
Early induction of secretoneurin expression following kainic acid administration at convulsant doses in the rat and gerbil hippocampus. | 2002 |
|
Spontaneous and precipitated withdrawal after chronic intragastric administration of gamma-hydroxybutyrate (GHB) in baboons. | 2005 May |
|
Antidepressant-like activity of CGP 36742 and CGP 51176, selective GABAB receptor antagonists, in rodents. | 2006 Nov |
|
Effects of GABAB receptor ligands in rodent tests of anxiety-like behavior. | 2007 Nov-Dec |
|
Hippocampal gene expression profiling reveals the possible involvement of Homer1 and GABA(B) receptors in scopolamine-induced amnesia. | 2007 Sep |
|
Cognitive enhancement by SGS742 in OF1 mice is linked to specific hippocampal protein expression. | 2008 Dec |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15451390
600 mg t.i.d. for 8 weeks
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18984654
IPSCs were evoked continuously (at 0.05 Hz, filtered at 3 kHz, digitized at 10 kHz) with a bipolar concentric stimulating electrode (SNEX-100, Rhodes Medical Instruments, Tujunga, CA) placed in the stratum radiatum of the CA1 region and was only interrupted when a tetanic stimulation (2 trains of 100 Hz for 1 s, 20-s interval) was delivered. Stimulation strengths (50–150 mA, 0.2 ms) were adjusted so that control IPSCs were ;50% of the maximum response, leaving adequate room for potentiation. Data for IPSCs were obtained from the average of two to five consecutive traces. Data for number of spontaneous IPSCs were collected in 3- to 5-min bins. Control responses had to be stable for 10–20 min before CGP-36742 (500 mM, for 10min) or tetanic stimulations were applied. Posttetanic responses were followed for $30 min. Both DNQX (20 mkM) and APV (40 mkM) were continually present in the recording medium.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
545416
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123690-78-8
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130021
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DTXSID10154063
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DB05010
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GBZ5UC0RME
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ACTIVE MOIETY