SKF-83959

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H20ClNO2
Molecular Weight	317.81
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC2=C(C=C(O)C(O)=C2Cl)C(C1)C3=CC(C)=CC=C3

InChI

InChIKey=JXMYTVOBSFOHAF-UHFFFAOYSA-N

InChI=1S/C18H20ClNO2/c1-11-4-3-5-12(8-11)15-10-20(2)7-6-13-14(15)9-16(21)18(22)17(13)19/h3-5,8-9,15,21-22H,6-7,10H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C18H20ClNO2
Molecular Weight	317.81
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1355737
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12675914 | https://www.ncbi.nlm.nih.gov/pubmed/17553535 | https://www.ncbi.nlm.nih.gov/pubmed/23892272

SKF83959 is a benzodiazepine derivative which acts as an agonist of D1 receptor. Activation of D1 receptors by SKF83959 fails to stimulate adenylyl cyclase and inhibits the stimulation of adenylyl cyclase induced by dopamine but stimulates phosphatidylinositol 4,5-biphosphate hydrolysis in membranes of frontal cortex. SKF83959 was identified as a specific agonist for the heteromer D1/D2 complex. SKF83959 elicit anti-parkinsonism effects in monkeys and rodents. In lower concentrations, SKF83959 inhibits serotonin, norepinephrine and dopamine transporters and is an allosteric regulator of sigma 1 receptor. The compound has demonstrated activity in a preclinical model of depression.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
D(1A) dopamine receptor 18 Target ID: P21728 Gene ID: 1812.0 Gene Symbol: DRD1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/1355737	Agonist 2678	0.66 nM [IC50]
Sigma non-opioid intracellular receptor 1 26 Target ID: Q99720\|\|\|Q7Z653 Gene ID: 10280.0 Gene Symbol: SIGMAR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23295385	Modulator 828
Sodium-dependent noradrenaline transporter 38 Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23892272	Inhibitor 8297	0.6 µM [Ki]
Sodium-dependent serotonin transporter 40 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23892272	Inhibitor 8297	1.43 µM [Ki]
Sodium-dependent dopamine transporter 42 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23892272	Inhibitor 8297	9.01 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17553535	Primary		Preclinical	Unknown Approved Use Unknown
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23892272	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.	2001 Apr 20	11334864
Ventral striatal vs. accumbal (shell) mechanisms and non-cyclase-coupled dopamine D(1)-like receptors in jaw movements.	2001 Jul 6	11448482
D5 dopamine receptors are required for dopaminergic activation of phospholipase C.	2009 Mar	19047479
Activation of phosphatidylinositol-linked novel D1 dopamine receptors inhibits high-voltage-activated Ca2+ currents in primary cultured striatal neurons.	2009 May	19225177
Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor.	2015 Apr 15	25660762

Patents

Sample Use Guides

In Vivo Use Guide

In a rat model of Parkinson's disease, SKF83959 was administered intraperitoneally at 0.5 mg/kg.

Route of Administration: Intraperitoneal

In Vitro Use Guide

[3H]SCH 23390 (72-80 Ci/mmol) was used as a radioligand to label dopamine D1 receptor. Rat striatal membranes were isolated in 50 mM K-phosphate buffer at pH 7.4 by homogenization and centrifugation. Membrane suspensions were incubated with 0.2 nM [3H]SCH23390 in a volume of 2.2 ml (1 mg original tissue) at 30°C for 60 min. After incubation, the samples were filtered through Whatman GF/F filters. Specific binding was defined as the difference in radioactivity obtained in the absence and the presence of 0.1 uM of cis(Z)-flupentixol. SKF83959 displaced [3H]SCH 23390 with IC50 of 0.66 nM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:20:14 GMT 2023` Edited by `admin` on `Sat Dec 16 11:20:14 GMT 2023`
Record UNII	8CJ9F3C4Q0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SKF-83959

Common Name

English

6-CHLORO-2,3,4,5-TETRAHYDRO-3-METHYL-1-(3-METHYLPHENYL)-1H-3-BENZAZEPINE-7,8-DIOL

Systematic Name

English

1H-3-BENZAZEPINE-7,8-DIOL, 6-CHLORO-2,3,4,5-TETRAHYDRO-3-METHYL-1-(3-METHYLPHENYL)-

Systematic Name

English

J489.412J

Code

English

Code System Code Type Description

WIKIPEDIA

SKF-83,959