Ketanserin

Ketanserin (R41468) is a drug with affinity for multiple G protein-coupled receptors (GPCR). Initially it was believed to be a highly selective antagonist for serotonin 5-HT_2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT_2A receptors over 5-HT_2C receptors (~20-30 fold). Ketanserin also has high affinity for alpha-1 adrenergic receptors, and very high affinity for histamine H1 receptors. Therefore, ketanserin can not be used to reliably discriminate between the effects of 5-HT_2A and 5-HT_2C receptors when both are present in an experimental system. Furthermore, when alpha-1 and H1 receptors are present, the effects of ketanserin can potentially represent a complex interaction of serotonin, adrenergic, and histamine receptor systems. Complicating the matter further is the fact that ketanserin has moderate affinity for alpha-2 adrenergic (~200 nM) and 5-HT₆ (~300 nM) receptors as well as weak affinity for dopamine D1 and D2 receptors (~300 nM and ~500 nM respectively). Ketanserin at levels of 500 nM or greater are thus potentially affecting at least 8 different GPCRs from 4 different families. (All affinity levels taken from the NIMH Psychoactive Drug Screening Program database )