SKF-83,959

SKF-83,959

Systematic (IUPAC) name
6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
Identifiers
PubChem	CID 24278699
ChemSpider	10131933
ChEMBL	CHEMBL520992
Chemical data
Formula	C18H20ClNO2
Molar mass	317.810 g/mol
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
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SKF-83,959 is a synthetic benzazepine derivative used in scientific research which acts as an agonist at the D₁-D₂ dopamine receptor.^[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 is a racemate that consists of the R-(+)- and S-(−)-enantiomers MCL 202 and MCL 201, respectively. SKF-83,959 inhibits sodium channels^[3] as well as delayed rectifier potassium channels.^[4]

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. 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.
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.
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. doi:10.1371/journal.pone.0005811. PMC 2690691. PMID 19503734.

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: 9–17. doi:10.1124/jpet.114.214411. 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. PMID 24929112.