Ketanserin

Ketanserin 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-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C 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-HT2A and 5-HT2C 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 )

Receptors for which ketanserin has high affinity binding:
 * 5-HT2A = 2-3 nM (rat and human)
 * 5-HT2C = 50 nM (rat), 100 nM (human)
 * alpha-1 adrenergic = ~40 nM
 * Histamine H1 = 2 nM

Solubility:
 * 6 mg/mL 0.1 M HCl
 * 10 mM H20
 * 3.3 mg/mL ethanol
 * 52 mg/mL DMSO

Ketanserin was discovered at Janssen Pharmaceutica in 1980.

Antihypertensive
It is classified as an antihypertensive by the World Health Organization and the National Institute of Health.

It has been used to reverse hypertension caused by protamine (which in turn was administered to reverse the effects of heparin overdose).

The reduction in hypertension is not associated with reflex tachycardia.

It has been used in cardiac surgery.

As a radioligand
With tritium (3H) radioactively labeled ketanserin is used as a radioligand for the serotonin 5-HT2A receptor, e.g. in receptor binding assays and autoradiography. This radiolabeling enables the study of the serotonin-2A receptor distribution in the human brain.

An autoradiography study of the human cerebellum has found an increasing binding of H-3-ketanserin with age (from below 50 femtomol per milligram tissue at around 30 years og age to over 100 above 75 years). The same research team found no significant correlation with age in their homogenate binding study.