Ketanserin


Ketanserin is a drug used clinically as an antihypertensive agent and in scientific research to study the serotonin system; specifically, the 5-HT2 receptor family. It was discovered at Janssen Pharmaceutica in 1980.

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.
The reduction in hypertension is not associated with reflex tachycardia.
It has been used in cardiac surgery.
A 2000 Cochrane Review found that, compared to placebo, ketanserin did not provide significant relief for people suffering from Raynaud's phenomenon attacks in the setting of progressive systemic sclerosis. While the frequency of the attacks was unaffected by ketanserin, there was a reduction in the duration of the individual attacks. However, due to the significant adverse effect burden, the authors concluded that ketanserin's utility for this indication is likely unbeneficial.

Research use

With tritium 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-HT2A receptor distribution in the human brain.
An autoradiography study of the human cerebellum has found an increasing binding of 3H-ketanserin with age. The same research team found no significant correlation with age in their homogenate binding study.
Ketanserin has also been used with carbon 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 Ki values of 2–3 nM for the 5-HT2A receptor and 28 nM for the 5-HT2C receptor). In primates including humans however, ketanserin is a more selective antagonist of the 5-HT2A over the 5-HT2C receptor, with Ki values of 2–3 nM for the 5-HT2Areceptor and 130 nM for the 5-HT2C receptor. In addition to the 5-HT2 receptors, ketanserin is also a high affinity antagonist for the H1 receptor, 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.