SKF-83,959 explained

SKF-83,959, a synthetic benzazepine derivative used in scientific research, 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.^[6]

Further reading

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

Notes and References

1. Rashid AJ, So CH, Kong MM, etal . 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 . 2007 . 17194762 . 1766439 . 10.1073/pnas.0604049104 . 2007PNAS..104..654R . free .
2. Guo L, Zhao J, Jin G, etal . SKF83959 is a potent allosteric modulator of sigma-1 receptor . Mol. Pharmacol. . 83 . 3 . 577–86 . 2013 . 23295385 . 10.1124/mol.112.083840 . 5848058 .
3. Chu HY, Wu Q, Zhou S, etal . SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism . J. Neurosci. Res. . 89 . 8 . 1259–66 . 2011 . 21538463 . 10.1002/jnr.22653 . 43869359 .
4. Chen XQ, Zhang J, Neumeyer JL, etal . Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects . PLOS ONE . 4 . 6 . e5811 . 2009 . 19503734 . 2690691 . 10.1371/journal.pone.0005811 . 2009PLoSO...4.5811C . free .
5. ((Fang, X.)), ((Guo, L.)), ((Jia, J.)), ((Jin, G.)), ((Zhao, B.)), ((Zheng, Y.)), ((Li, J.)), ((Zhang, A.)), ((Zhen, X.)) . Acta Pharmacologica Sinica . SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity . 34 . 9 . 1149–1155 . September 2013 . 1671-4083 . 10.1038/aps.2013.66. 23892272 . 4003162 . free .
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.)) . Journal of Medicinal Chemistry . Dopaminergic activity of substituted 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines . 25 . 4 . 352–358 . April 1982 . 10.1021/jm00346a005. 7069713 .