SKF-83,959

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−1
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.^[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]

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.

SKF-83,959

References

Further reading