Misplaced Pages

SKF-83,959

Identifiers
IUPAC name 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
CAS Number	67287-95-0
PubChem CID	11957685
ChemSpider	10131933
UNII	8CJ9F3C4Q0
ChEBI	CHEBI:63996
ChEMBL	ChEMBL520992
Chemical and physical data
Formula	C18H20ClNO2
Molar mass	317.81 g·mol
3D model (JSmol)	Interactive image
SMILES Br.Clc1c3c(cc(O)c1O)C(c2cccc(c2)C)CN(CC3)C
InChI 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 Key:FHYWNBUFNGHNCP-UHFFFAOYSA-N
(verify)

SKF-83,959, a synthetic benzazepine derivative used in scientific research, acts as an agonist at the D₁–D₂ dopamine receptor heteromer. 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. SKF-83,959 additionally inhibits sodium channels as well as delayed rectifier potassium channels. 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. The synthesis has been described.

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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

• Lee SM, Yang Y, Mailman RB (2014). "Dopamine D1 receptor signaling: Does GαQ-phospholipase C actually play a role?". J. Pharmacol. Exp. Ther. 351 (1): 9–17. doi:10.1124/jpet.114.214411. PMC 4165024. PMID 25052835.
• Lee SM, Kant A, Blake D, et al. (2014). "SKF-83959 is not a highly-biased functionally selective D1 dopamine receptor ligand with activity at phospholipase C". Neuropharmacology. 86: 145–54. doi:10.1016/j.neuropharm.2014.05.042. PMC 4188748. PMID 24929112.

This drug article relating to the nervous system is a stub. You can help Misplaced Pages by expanding it.

• v
• t
• e

• 1-Phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
• Drugs developed by GSK plc
• D1-receptor agonists
• D2-receptor agonists
• Catechols
• Chloroarenes
• Potassium channel blockers
• Receptor heteromer ligands
• Sigma receptor ligands
• Sodium channel blockers
• Nervous system drug stubs