SB-221284

SB-221284 is a selective serotonin 5-HT_2C and 5-HT_2B receptor antagonist which is used in scientific research.^[1][2][3]

SB-221284

Clinical data
Other names	SB221284
Drug class	Serotonin 5-HT2C receptor antagonist; Serotonin 5-HT2B receptor antagonist
Identifiers
IUPAC name 5-methylsulfanyl-N-pyridin-3-yl-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
CAS Number	196965-14-7
PubChem CID	443389
IUPHAR/BPS	191
ChemSpider	391618
KEGG	C11741
ChEBI	CHEBI:8978
ChEMBL	ChEMBL276140
CompTox Dashboard (EPA)	DTXSID50332080
Chemical and physical data
Formula	C16H14F3N3OS
Molar mass	353.36 g·mol−1
3D model (JSmol)	Interactive image
SMILES CSC1=C(C=C2C(=C1)CCN2C(=O)NC3=CN=CC=C3)C(F)(F)F
InChI InChI=1S/C16H14F3N3OS/c1-24-14-7-10-4-6-22(13(10)8-12(14)16(17,18)19)15(23)21-11-3-2-5-20-9-11/h2-3,5,7-9H,4,6H2,1H3,(H,21,23) Key:OQZOXHCRSXYSPM-UHFFFAOYSA-N

Its affinities (K_i) are 2.2 to 2.5 nM for the serotonin 5-HT_2C receptor, 2.5 to 12.6 nM for the serotonin 5-HT_2B receptor, and 398 to 550 nM for the serotonin 5-HT_2A receptor (where it is also an antagonist).^[2][4][3][5] The drug has 160- to 250-fold selectivity for the serotonin 5-HT_2C receptor over the serotonin 5-HT_2A receptor.^[1][4][3] It is said to have been the first serotonin 5-HT_2C receptor ligand to show 100-fold selectivity over the serotonin 5-HT_2A receptor.^[6]

SB-221284 has shown anxiolytic-like effects in animals.^[1][5][7][8] Conversely, it has been said to be inactive in terms of antidepressant-like, antiobsessional-like, antipanic-like, and sedative effects.^[1][8] It also showed no proconvulsant or hyperphagic effects in animals, phenotypes that are notably observed with serotonin 5-HT_2C receptor knockout.^[3]

The preferential serotonin 5-HT_2C receptor agonist meta-chlorophenylpiperazine (mCPP) and the serotonin reuptake inhibitor fluoxetine have been found to acutely reduce social interaction in rodents.^[4] SB-221284 was found to reverse the acute decreases in social interaction produced by mCPP and fluoxetine.^[4] The drug has also been found to block mCPP-induced hypolocomotion.^[1][5][7][9] Both SB-221284 and the selective serotonin 5-HT_2C receptor antagonist SB-242084 have been found to enhance the nucleus accumbens dopamine release and hyperlocomotion induced by NMDA receptor antagonists like phencyclidine (PCP) and dizocilpine (MK-801).^[9] Conversely, both drugs had no effect on locomotor activity or dopamine release in the nucleus accumbens by themselves.^[9] However, another study reported that SB-221284 by itself did enhance locomotion.^[4]

SB-221284 was first described in the scientific literature by 1996.^[10][3] It was researched by GlaxoSmithKline as a possible non-sedating anxiolytic and reached the preclinical research stage of development.^{[5][11][12][3]} However, it was found to be a potent inhibitor of a number of human cytochrome P450 enzymes (particularly CYP1A2), which precluded further development of the drug.^[1][12][3] Other sources have stated that SB-221284 was not further developed due to "toxicity"^[10] and that other drugs were pursued instead as SB-221284 was a "fairly weak" serotonin 5-HT_2C receptor antagonist.^[6]