Ketanserin

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Ketanserin
Systematic (IUPAC) name
 ?
Identifiers
CAS number 74050-98-9
ATC code C02KD01
PubChem 3822
Chemical data
Formula C22FN3O3 
Mol. mass 395.43 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?

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Routes  ?

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Ketanserin (R41468) is a drug with affinity for multiple G protein-coupled receptors (GPCR). It is a highly selective antagonist for serotonin 5-HT2A receptors, but also has moderate selectivity for 5-HT2C receptors and 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 delta-1t adrenergic receptor (~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 [1])

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.

Uses

Antihypertensive

It is classified as an antihypertensive by the World Health Organization[2] and the National Institute of Health.[3]

It has been used to reverse hypertension caused by protamine (which in turn was administered to reverse the effects of heparin overdose).[4]

The reduction in hypertension is not associated with reflex tachycardia.[5]

It has been used in cardiac surgery.[6]

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.[7] This radiolabeling enables the study of the serotonin-2A receptor distribution in the human brain.[8]

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).[9] The same research team found no significant correlation with age in their homogenate binding study.

As a Blocker with Another Radioligand

Ketanserin has also been used with carbon (11C) radioactively labeled NNC112 in order to image cortical D1 receptors without contamination by 5-HT2A receptors.[10]

See Also

References

  1. NIMH Psychoactive Drug Screening Program
  2. ATC/DDD Index
  3. Ketanserin
  4. van der Starre PJ, Solinas C (1996). "Ketanserin in the treatment of protamine-induced pulmonary hypertension". Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 23 (4): 301–4. PMID 8969033.
  5. Hodsman NB, Colvin JR, Kenny GN (May 1989). "Effect of ketanserin on sodium nitroprusside requirements, arterial pressure control and heart rate following coronary artery bypass surgery". British journal of anaesthesia 62 (5): 527–31. doi:10.1093/bja/62.5.527. PMID 2786422.
  6. Elbers PW, Ozdemir A, van Iterson M, van Dongen EP, Ince C (December 2008). "Microcirculatory Imaging in Cardiac Anesthesia: Ketanserin Reduces Blood Pressure But Not Perfused Capillary Density". J. Cardiothorac. Vasc. Anesth. 23 (1): 95–101. doi:10.1053/j.jvca.2008.09.013. PMID 19058975.
  7. Simon B. Eickhoff, Axel Schleicher, Filip Scheperjans, Nicola Palomero-Gallagher & Karl Zilles (2007). "Analysis of neurotransmitter receptor distribution patterns in the cerebral cortex". NeuroImage 34 (4): 1317–1330. doi:10.1016/j.neuroimage.2006.11.016. PMID 17182260.
  8. A. Pazos, A. Probst, J. M. Palacios (1987). "Serotonin receptors in the Human Brain—IV. Autoradiographic mapping of serotonin-2 receptors". Neuroscience 21 (1): 123–139. doi:10.1016/0306-4522(87)90327-7. PMID 3601071.
  9. Sharon L. Eastwood, Philip W. J. Burnet, Rebecca Gittins, Kate Baker, Paul J. Harrison (November 2001). "Expression of serotonin 5-HT2A receptors in the human cerebellum and alterations in schizophrenia". Synapse 42 (2): 104–114. doi:10.1002/syn.1106. PMID 11574947.
  10. Catafau AM, Searle GE, Bullich S, Gunn RN, Rabiner EA, Herance R, Radua J, Farre M, Laruelle M. (2010). "Imaging cortical dopamine D1 receptors using 11C NNC112 and ketanserin blockade of the 5-HT 2A receptors". J Cereb Blood Flow Metab 30: 985–93. doi:10.1038/jcbfm.2009.269.

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