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

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	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Agonist 2,752	0.66 nM [IC50]
Sigma non-opioid intracellular receptor 1 26	Modulator 846
Sodium-dependent noradrenaline transporter 39	Inhibitor 8,504	0.6 µM [Ki]
Sodium-dependent serotonin transporter 41	Inhibitor 8,504	1.43 µM [Ki]
Sodium-dependent dopamine transporter 43	Inhibitor 8,504	9.01 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 232	Primary		Preclinical	Unknown
Depression 240	Primary		Preclinical	Unknown

PubMed

Show entries

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
Prefrontal, accumbal [shell] and ventral striatal mechanisms in jaw movements and non-cyclase-coupled dopamine D1-like receptors.	2003 Jul 18	12877937
Regulation of cyclin-dependent kinase 5 and calcium/calmodulin-dependent protein kinase II by phosphatidylinositol-linked dopamine receptor in rat brain.	2004 Dec	15286209
Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys.	2004 Jan	14563783

Showing 1 to 5 of 10 entries

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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.