Ketanserin

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Ketanserin
Ketanserin.png
Systematic (IUPAC) name
3-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}quinazoline-2,4(1H,3H)-dione
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
?
Identifiers
CAS number 74050-98-9 YesY
ATC code C02KD01 QD03AX90
PubChem CID 3822
IUPHAR ligand 88
ChemSpider 3690 YesY
UNII 97F9DE4CT4 YesY
KEGG D02363 YesY
ChEBI CHEBI:6123 N
ChEMBL CHEMBL51 YesY
Chemical data
Formula C22H22FN3O3 
Molecular mass 395.43 g/mol
 N (what is this?)  (verify)

Ketanserin (INN, USAN, BAN) (brand name Sufrexal; former code name R41468) is a drug used clinically as an antihypertensive agent and in scientific research to study the serotonin system; specifically, the 5-HT2A receptor.[1] It was discovered at Janssen Pharmaceutica in 1980.

Uses[edit]

Antihypertensive[edit]

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[edit]

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[edit]

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]

Pharmacology[edit]

Ketanserin is a high-affinity antagonist of the 5-HT2A receptor (Ki = 2-3 nM).[11][12] However, it also blocks the H1 receptor with high affinity (Ki = 2 nM).[13][12] In addition, ketanserin less potently antagonizes the α1-adrenergic (Ki = ~40 nM),[13] α2-adrenergic = ~200 nM), 5-HT1D (Ki = ? nM),[11][14] 5-HT2B (Ki = ? nM),[15] 5-HT2C (Ki = 100 nM),[13] 5-HT6 (Ki = ~300 nM),[16] 5-HT7 (Ki = ? nM),[11] D1 (~300 nM),[13] and D2 (Ki = ~500 nM) receptors.[13][12] It also blocks the vesicular monoamine transporter (VMAT).[17][18]

See also[edit]

References[edit]

  1. ^ Gopi Doctor Ahuja (2005). Drug Injury: Liability, Analysis, and Prevention. Lawyers & Judges Publishing Company. pp. 304–. ISBN 978-0-913875-27-8. 
  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. PMC 325377. 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 (5): 985–93. doi:10.1038/jcbfm.2009.269. PMID 20029452. 
  11. ^ a b c Alfredo Meneses (11 March 2014). The Role of 5-HT Systems on Memory and Dysfunctional Memory: Emergent Targets for Memory Formation and Memory Alterations. Elsevier Science. pp. 23–. ISBN 978-0-12-801083-9. 
  12. ^ a b c NIMH Psychoactive Drug Screening Program
  13. ^ a b c d e C.P. Coyne (9 January 2008). Comparative Diagnostic Pharmacology: Clinical and Research Applications in Living-System Models. John Wiley & Sons. pp. 104–. ISBN 978-0-470-34429-3. 
  14. ^ B. Olivier; I. van Wijngaarden; W. Soudijn (10 July 1997). Serotonin Receptors and their Ligands. Elsevier. pp. 118–. ISBN 978-0-08-054111-2. 
  15. ^ Mark Chapman (2007). Evaluation of the Role of Serotonin in Pulmonary Arterial Hypertension in Broilers Induced by Bacterial Lipopolysaccharide and Cellulose Microparticles. ProQuest. pp. 31–. ISBN 978-0-549-36052-0. 
  16. ^ Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 388–. ISBN 978-1-60913-345-0. 
  17. ^ Christian P. Muller; Barry Jacobs (30 December 2009). Handbook of the Behavioral Neurobiology of Serotonin. Academic Press. pp. 592–. ISBN 978-0-08-087817-1. 
  18. ^ Catecholamines: Bridging Basic Science with Clinical Medicine: Bridging Basic Science with Clinical Medicine. Academic Press. 20 October 1997. pp. 237–. ISBN 978-0-08-058134-7.