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Chemical compound
SKF-83,959
6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
PubChem
CID
ChemSpider
UNII
ChEMBL
Formula C 18 H 20 Cl N O 2
Molar mass 317.81 g·mol−1 3D model (
JSmol )
Br.Clc1c3c(cc(O)c1O)C(c2cccc(c2)C)CN(CC3)C
InChI=1S/C18H20ClNO2.BrH/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;1H
Y Key:FHYWNBUFNGHNCP-UHFFFAOYSA-N
Y
(verify)
SKF-83,959 is a
synthetic
benzazepine
derivative used in
scientific research which acts as an
agonist at the
D1 –D2 dopamine receptor heteromer .
[1] It behaves as a
full agonist at the D1
protomer and a high-
affinity
partial agonist at the D2 protomer. It was further shown to act as an
allosteric modulator of the
sigma-1 receptor .
[2] SKF-83,959 additionally inhibits
sodium channels
[3] as well as delayed rectifier
potassium channels .
[4] SKF-83,959 is a
racemate that consists of the R -(+)- and S -(−)-
enantiomers MCL-202 and MCL-201, respectively.
SKF-83,959 was described as a
SNDRI .
[5] The synthesis has been described:[
sentence fragment ]
[6]
References
^ Rashid AJ, So CH, Kong MM, et al. (2007).
"D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum" . Proc. Natl. Acad. Sci. U.S.A . 104 (2): 654–9.
Bibcode :
2007PNAS..104..654R .
doi :
10.1073/pnas.0604049104 .
PMC
1766439 .
PMID
17194762 .
^ Guo L, Zhao J, Jin G, et al. (2013). "SKF83959 is a potent allosteric modulator of sigma-1 receptor". Mol. Pharmacol . 83 (3): 577–86.
doi :
10.1124/mol.112.083840 .
PMID
23295385 .
S2CID
5848058 .
^ Chu HY, Wu Q, Zhou S, et al. (2011). "SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism". J. Neurosci. Res . 89 (8): 1259–66.
doi :
10.1002/jnr.22653 .
PMID
21538463 .
S2CID
43869359 .
^ Chen XQ, Zhang J, Neumeyer JL, et al. (2009).
"Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects" . PLOS ONE . 4 (6): e5811.
Bibcode :
2009PLoSO...4.5811C .
doi :
10.1371/journal.pone.0005811 .
PMC
2690691 .
PMID
19503734 .
^ Fang, X., Guo, L., Jia, J., Jin, G., Zhao, B., Zheng, Y., Li, J., Zhang, A., Zhen, X. (September 2013).
"SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity" . Acta Pharmacologica Sinica . 34 (9): 1149–1155.
doi :
10.1038/aps.2013.66 .
ISSN
1671-4083 .
PMC
4003162 .
PMID
23892272 .
^ Pfeiffer, F. R., Wilson, J. W., Weinstock, J., Kuo, G. Y., Chambers, P. A., Holden, K. G., Hahn, R. A., Wardell, J. R., Alfonso, J. T. (April 1982). "Dopaminergic activity of substituted 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines". Journal of Medicinal Chemistry . 25 (4): 352–358.
doi :
10.1021/jm00346a005 .
PMID
7069713 .
Further reading
Calcium
VDCCs Tooltip Voltage-dependent calcium channels
Potassium
VGKCs Tooltip Voltage-gated potassium channels
IRKs Tooltip Inwardly rectifying potassium channel
KCa Tooltip Calcium-activated potassium channel
K2Ps Tooltip Tandem pore domain potassium channel
Sodium
VGSCs Tooltip Voltage-gated sodium channels
ENaC Tooltip Epithelial sodium channel
ASICs Tooltip Acid-sensing ion channel
Chloride
CaCCs Tooltip Calcium-activated chloride channel
CFTR Tooltip Cystic fibrosis transmembrane conductance regulator
Unsorted
Others
TRPs Tooltip Transient receptor potential channels
LGICs Tooltip Ligand gated ion channels