SB-221284
SB-221284 is a selective serotonin 5-HT2C and 5-HT2B receptor antagonist which is used in scientific research.
Its affinities are 2.2 to 2.5nM for the serotonin 5-HT2C receptor, 2.5 to 12.6nM for the serotonin 5-HT2B receptor, and 398 to 550nM for the serotonin 5-HT2A receptor. The drug has 160- to 250-fold selectivity for the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor. It is said to have been the first serotonin 5-HT2C receptor ligand to show 100-fold selectivity over the serotonin 5-HT2A receptor.
SB-221284 has shown anxiolytic-like effects in animals. Conversely, it has been said to be inactive in terms of antidepressant-like, antiobsessional-like, antipanic-like, and sedative effects. It also showed no proconvulsant or hyperphagic effects in animals, phenotypes that are notably observed with serotonin 5-HT2C receptor knockout.
The preferential serotonin 5-HT2C receptor agonist meta-chlorophenylpiperazine and the serotonin reuptake inhibitor fluoxetine have been found to acutely reduce social interaction in rodents. SB-221284 was found to reverse the acute decreases in social interaction produced by mCPP and fluoxetine. The drug has also been found to block mCPP-induced hypolocomotion. Both SB-221284 and the selective serotonin 5-HT2C receptor antagonist SB-242084 have been found to enhance the nucleus accumbens dopamine release and hyperlocomotion induced by NMDA receptor antagonists like phencyclidine and dizocilpine. Conversely, both drugs had no effect on locomotor activity or dopamine release in the nucleus accumbens by themselves. However, another study reported that SB-221284 by itself did enhance locomotion.
SB-221284 was first described in the scientific literature by 1996. It was researched by GlaxoSmithKline as a possible non-sedating anxiolytic and reached the preclinical research stage of development. However, it was found to be a potent inhibitor of a number of human cytochrome P450 enzymes, which precluded further development of the drug. Other sources have stated that SB-221284 was not further developed due to "toxicity" and that other drugs were pursued instead as SB-221284 was a "fairly weak" serotonin 5-HT2C receptor antagonist.