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 2752	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 846
Sodium-dependent noradrenaline transporter 39 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 8504	0.6 µM [Ki]
Sodium-dependent serotonin transporter 41 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 8504	1.43 µM [Ki]
Sodium-dependent dopamine transporter 43 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 8504	9.01 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17553535	Primary		Preclinical	Unknown Approved Use Unknown
Depression 240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23892272	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor.	2015-04-15	25660762
Activation of phosphatidylinositol-linked novel D1 dopamine receptors inhibits high-voltage-activated Ca2+ currents in primary cultured striatal neurons.	2009-05	19225177
D5 dopamine receptors are required for dopaminergic activation of phospholipase C.	2009-03	19047479
Activity-dependent modulation of limbic dopamine D3 receptors by CaMKII.	2009-02-12	19217379
Dopamine profoundly suppresses excitatory transmission in neonatal rat hippocampus via phosphatidylinositol-linked D1-like receptor.	2006	16406680
Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists.	2005-10	15985612
Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions.	2004-12	15292458
Regulation of cyclin-dependent kinase 5 and calcium/calmodulin-dependent protein kinase II by phosphatidylinositol-linked dopamine receptor in rat brain.	2004-12	15286209
Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys.	2004-01	14563783
Prefrontal, accumbal [shell] and ventral striatal mechanisms in jaw movements and non-cyclase-coupled dopamine D1-like receptors.	2003-07-18	12877937
Ventral striatal vs. accumbal (shell) mechanisms and non-cyclase-coupled dopamine D(1)-like receptors in jaw movements.	2001-07-06	11448482
Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.	2001-04-20	11334864

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 `Tue Apr 01 16:21:04 GMT 2025` Edited by `admin` on `Tue Apr 01 16:21:04 GMT 2025`
Record UNII	8CJ9F3C4Q0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SKF-83959

Common Name

English

J489.412J

Preferred 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

Code System Code Type Description

WIKIPEDIA

SKF-83,959