Ketanserin

Medical use

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

It has been used to reverse pulmonary 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.

Research use

With tritium (³H) radioactively labeled ketanserin is used as a radioligand for serotonin 5-HT₂ receptors, e.g. in receptor binding assays and autoradiography. This radio-labeling has enabled the study of serotonin 5-HT_2A receptor distribution in the human brain.

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

Ketanserin has also been used with carbon (¹¹C) radioactively labeled NNC112 in order to image cortical D₁ receptors without contamination by 5-HT₂ receptors.

Pharmacology

Ketanserin is a high-affinity non-selective antagonist of 5-HT₂ receptors in rodents, with K_i values of 2–3 nM for the 5-HT_2A receptor and 28 nM for the 5-HT_2C receptor). In primates including humans however, ketanserin is a more selective antagonist of the 5-HT_2A over the 5-HT_2C receptor, with K_i values of 2–3 nM for the 5-HT_2Areceptor and 130 nM for the 5-HT_2C receptor. In addition to the 5-HT₂ receptors, ketanserin is also a high affinity antagonist for the H₁ receptor (K_i = 2 nM), and has measurable albeit relatively low affinity for a number of other receptors:

It has also been found to block the vesicular monoamine transporter 2 (VMAT2).