SB-247853 is a highly selective serotonin 5-HT<sub>2C</sub> receptor inverse agonist which was under development for the treatment of major depressive disorder but was never marketed.
Its affinities (K<sub>i</sub>) were found to be 0.50nM for the serotonin 5-HT<sub>2C</sub> receptor, 60nM for the serotonin 5-HT<sub>2B</sub> receptor, and 1,300nM for the serotonin 5-HT<sub>2A</sub> receptor. Hence, it shows 120-fold selectivity for the serotonin 5-HT<sub>2C</sub> receptor over the serotonin 5-HT<sub>2B</sub> receptor and 2,600-fold selectivity for the serotonin 5-HT<sub>2C</sub> receptor over the serotonin 5-HT<sub>2A</sub> receptor. The drug reverses the hypolocomotion induced by the serotonin 5-HT<sub>2C</sub> receptor agonist meta-chlorophenylpiperazine (mCPP) in rodents. It is orally active.
The drug produced orthostatic intolerance in healthy human volunteers during the first dose-escalation clinical study. Subsequently, it was found to cause substantial hypotension (low blood pressure) and presyncope (pre-fainting symptoms) in the tilt table test. It was concluded based on these findings that the serotonin 5-HT<sub>2C</sub> receptor is involved in regulating the cardiovascular system.
SB-247853 was first described in the scientific literature by 2000. It was developed by GlaxoSmithKline. The drug reached phase 1 clinical trials prior to the discontinuation of its development in 2005.