RS-102221

RS-102221
Clinical data
Other names	RS-102,221; 8-[5-(2,4-Dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl -5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione
Identifiers
	IUPAC name N-{5-[5-(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)pentanoyl] -2,4-dimethoxyphenyl}-4-(trifluoromethyl)benzenesulfonamide;
CAS Number	185376-97-0 ;
PubChem CID	3693566;
IUPHAR/BPS	187;
ChemSpider	2925610;
ChEMBL	ChEMBL88402 ;
CompTox Dashboard (EPA)	DTXSID801028164 ;
Chemical and physical data
Formula	C27H33F3N4O7S
Molar mass	614.64 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c4cc(C(F)(F)F)ccc4S(=O)(=O)Nc(c(OC)cc2OC)cc2C(=O)CCCCN(CC3)CCC13NC(=O)NC1=O;
	InChI InChI=1S/C27H31F3N4O7S/c1-40-22-16-23(41-2)20(33-42(38,39)18-8-6-17(7-9-18)27(28,29)30)15-19(22)21(35)5-3-4-12-34-13-10-26(11-14-34)24(36)31-25(37)32-26/h6-9,15-16,33H,3-5,10-14H2,1-2H3,(H2,31,32,36,37); Key:HZZZZODVDSHQRG-UHFFFAOYSA-N;
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RS-102221 is a drug developed by Hoffmann–La Roche, which was one of the first compounds discovered that acts as a potent and selective antagonist at the serotonin 5-HT_2C receptor, with around 100× selectivity over the closely related 5-HT_2A and 5-HT_2B receptors.^[1] It has anxiolytic effects in animal studies,^[2] increases the effectiveness of SSRI antidepressants,^[3] and shows a complex interaction with cocaine, increasing some effects but decreasing others, reflecting a role for the 5-HT_2C receptor in regulation of the dopamine signalling system in the brain.^[4]^[5]^[6]^[7]

References

^ Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, et al. (1997). "RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist". Neuropharmacology. 36 (4–5): 621–9. doi:10.1016/s0028-3908(97)00049-x. PMID 9225287. S2CID 24930608.
^ Kuznetsova EG, Amstislavskaya TG, Shefer EA, Popova NK (July 2006). "Effect of 5-HT2C receptor antagonist RS 102221 on mouse behavior". Bulletin of Experimental Biology and Medicine. 142 (1): 76–9. doi:10.1007/s10517-006-0296-8. PMID 17369908. S2CID 36424571.
^ Cremers TI, Giorgetti M, Bosker FJ, Hogg S, Arnt J, Mørk A, et al. (October 2004). "Inactivation of 5-HT(2C) receptors potentiates consequences of serotonin reuptake blockade". Neuropsychopharmacology. 29 (10): 1782–9. doi:10.1038/sj.npp.1300474. PMID 15138437.
^ Filip M, Cunningham KA (April 2002). "Serotonin 5-HT(2C) receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine". Pharmacology, Biochemistry, and Behavior. 71 (4): 745–56. doi:10.1016/s0091-3057(01)00741-9. PMID 11888566. S2CID 292398.
^ Filip M, Cunningham KA (August 2003). "Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex". The Journal of Pharmacology and Experimental Therapeutics. 306 (2): 734–43. doi:10.1124/jpet.102.045716. PMID 12721337. S2CID 8338748.
^ Morita K, Hamamoto M, Arai S, Kitayama S, Irifune M, Kawahara M, et al. (September 2005). "Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities" (PDF). Brain Research. 1057 (1–2): 153–60. doi:10.1016/j.brainres.2005.07.049. PMID 16125150. S2CID 30437231.
^ Dremencov E, Weizmann Y, Kinor N, Gispan-Herman I, Yadid G (February 2006). "Modulation of dopamine transmission by 5HT2C and 5HT3 receptors: a role in the antidepressant response". Current Drug Targets. 7 (2): 165–75. doi:10.2174/138945006775515491. PMID 16475958.

[1] Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, et al. (1997). "RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist". Neuropharmacology. 36 (4–5): 621–9. doi:10.1016/s0028-3908(97)00049-x. PMID 9225287. S2CID 24930608.

[2] Kuznetsova EG, Amstislavskaya TG, Shefer EA, Popova NK (July 2006). "Effect of 5-HT2C receptor antagonist RS 102221 on mouse behavior". Bulletin of Experimental Biology and Medicine. 142 (1): 76–9. doi:10.1007/s10517-006-0296-8. PMID 17369908. S2CID 36424571.

[3] Cremers TI, Giorgetti M, Bosker FJ, Hogg S, Arnt J, Mørk A, et al. (October 2004). "Inactivation of 5-HT(2C) receptors potentiates consequences of serotonin reuptake blockade". Neuropsychopharmacology. 29 (10): 1782–9. doi:10.1038/sj.npp.1300474. PMID 15138437.

[4] Filip M, Cunningham KA (April 2002). "Serotonin 5-HT(2C) receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine". Pharmacology, Biochemistry, and Behavior. 71 (4): 745–56. doi:10.1016/s0091-3057(01)00741-9. PMID 11888566. S2CID 292398.

[5] Filip M, Cunningham KA (August 2003). "Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex". The Journal of Pharmacology and Experimental Therapeutics. 306 (2): 734–43. doi:10.1124/jpet.102.045716. PMID 12721337. S2CID 8338748.

[6] Morita K, Hamamoto M, Arai S, Kitayama S, Irifune M, Kawahara M, et al. (September 2005). "Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities" (PDF). Brain Research. 1057 (1–2): 153–60. doi:10.1016/j.brainres.2005.07.049. PMID 16125150. S2CID 30437231.

[7] Dremencov E, Weizmann Y, Kinor N, Gispan-Herman I, Yadid G (February 2006). "Modulation of dopamine transmission by 5HT2C and 5HT3 receptors: a role in the antidepressant response". Current Drug Targets. 7 (2): 165–75. doi:10.2174/138945006775515491. PMID 16475958.

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See also

References