Altanserin

drugbox
IUPAC_name = 3- [2- [4-(4-fluorobenzoyl)piperidin-1-yl] ethyl] -2-sulfanylidene-1H-quinazolin-4-one

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CAS_number = 76330-71-7
ATC_prefix =
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PubChem = 3033677
DrugBank =
C=22|H=22|F=1|N=3|O=2|S=1
molecular_weight = 411.49ABX, [http://www.abx.de/chemicals/1810.pdf Altanserin] , Radeberg, Germany.]
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Altanserin is a compound that binds to the 5-HT_2A receptor (serotonin 2A receptor). It is a yellowish solid.Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography (PET) studies of the brain, i.e., studies of the serotonin-2A neuroreceptors.Besides human neuroimaging studies altanserin has also been used in the study of rats. [Cite journal
author = Christian Lemaire, R. Cantineau, M. Guillaume, A. Plenevaux, Leon Christiaens
title = Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats
journal = Journal of Nuclear Medicine
year = 1991
month = December
volume = 32
pages = 2266–2277
pmid = 1744713
url = http://jnm.snmjournals.org/cgi/reprint/32/12/2266] [Cite journal
author = F. Biver, F. Lotstra, M. Monclus, S. Dethy, P. Damhaut, D. Wikler, A. Luxen and S. Goldman
title = "In vivo" binding of [¹⁸F] altanserin to rat brain 5HT₂ receptors: A film and electronic autoradiographic study
journal = Nuclear Medicine and Biology
volume = 24
issue = 4
month = May
year = 1997
pages = 357–360
doi = 10.1016/S0969-8051(97)00054-1
pmid = 9257335]

An alternative for PET imaging the 5-HT_2A receptor is the ¹¹CMDL 100,907 radioligand.Fluorine-18-altanserin and tritium-MDL 100,907 have shown very comparable binding.Cite journal
author = Heidi Kristiansen, Bettina Elfving, Per Plenge, Lars H. Pinborg, Nic Gillings & Gitte Moos Knudsen
title = Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907
journal = Synapse
year = 2005
month = December
volume = 58
issue = 4
pages = 249–257
url = http://www3.interscience.wiley.com/cgi-bin/abstract/112098314/ABSTRACT
doi = 10.1002/syn.20205] Both altanserin and MDL 100,907 are 5-HT_2A receptor antagonists. [¹⁸F] -setoperone can also be used in PET.

An alternative SPECT radioligand is the [¹²³I] -5-I-R91150 receptor antagonist.Cite journal
author = Kurt Audenaert, Koen Van Laere, Filip Dumont, Miriam Vervaet, Ingeborg Goethals, Guido Slegers, John Mertens, Cees van Heeringen, Rudi A. Dierckx
title = Decreased 5-HT_2A Receptor Binding in Patients with Anorexia Nervosa
journal = Journal of Nuclear Medicine
volume = 44
pages = 163–169 ]

A rapid chemical synthesis of fluorine-18 and H-2 dual-labeled altanserin has been described. [Cite journal
author = Ping-Zhong Tan, Ronald M. Baldwin, Tao Fu, Dennis S. Charney, Robert B. Innis
title = Rapid synthesis of F-18 and H-2 dual-labeled altanserin, a metabolically resistant PET ligand for 5-HT_2a receptors
journal = Journal of Labelled Compounds and Radiopharmaceuticals
volume = 42
issue = 5
pages = 457–467
year = 1999
month = May
doi = 10.1002/(SICI)1099-1344(199905)42:5<457::AID-JLCR206>3.0.CO;2-0
doilabel = 10.1002/(SICI)1099-1344(199905)42:5457::AID-JLCR2063.0.CO;2-0]

Other ligands for other parts of the serotonin system used in PET studies are, e.g., DASB, ketanserin and WAY-100635.

Human brain mapping studies with altanserin

As of 2007 altanserin is probably not used in clinical routine. However, there have been performed several research-based neuroimaging studies with the compound in humans since the 1990's. [Cite journal
author = Frangoise Biver, Serge Goldman, André Luxen, Michel Monclus, Manuel Forestini, Julien Mendlewicz and Françoise Lotstra
title = Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography
journal = European Journal of Nuclear Medicine and Molecular Imaging
volume = 21
issue = 9
month = September
year = 1994
doi = 10.1007/BF00238117
pages = 937&ndash;946
url = http://www.springerlink.com/content/j063h72754286373/] [Cite journal
author = Sadzot B, Lemaire C, Maquet P, Salmon E, Plenevaux A, Degueldre C, Hermanne JP, Guillaume M, Cantineau R, Comar D, et al.
title = Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F] altanserin: results in young normal controls
journal = Journal of Cerebral Blood Flow and Metabolism
year = 1995
month = September
volume = 15
issue = 5
pages = 787&ndash;797
pmid = 7673371] Some of these studies have considered methodogical issues such as the reproducibility of the method [Cite journal
author = Gwenn S. Smith, Julie C. Price, Brian J. Lopresti, Yiyun Huang, Norman Simpson, Daniel Holt, N. Scott Mason, Carolyn Cidis Meltzer, Robert A. Sweet, Thomas Nichols, Donald Sashin, Chester A. Mathis
title = Test-retest variability of serotonin 5-HT_2A receptor binding measured with positron emission tomography and [¹⁸F] altanserin in the human brain
journal = Synapse
year = 1998
volume = 30
issue = 4
pages = 380&ndash;392
doi = 10.1002/(SICI)1098-2396(199812)30:4<380::AID-SYN5>3.0.CO;2-U
doilabel = 10.1002/(SICI)1098-2396(199812)30:4380::AID-SYN53.0.CO;2-U] [Cite journal
author = Steven Haugbøl, Lars H. Pinborg, Haroon M. Arfan, Vibe Frøkjær, Jacob Madsen, Tim B. Dyrby, Claus Svarer and Gitte M. Knudsen
title = Reproducibility of 5-HT_2A receptor measurements and sample size estimations with [¹⁸F] altanserin PET using a bolus/infusion approach
journal = European Journal of Nuclear Medicine and Molecular Imaging
volume = 34
issue = 6
month = June
year = 2007
pages = 910&ndash;915
doi = 10.1007/s00259-006-0296-y] or whether to use constant infusion [Cite journal
author = Christopher H. van Dyck, Ping-Zhong Tan, Ronald M. Baldwin, Louis A. Amici, Pradeep K. Garg, Chin K. Ng, Robert Soufer, Dennis S. Charney and Robert B. Innis
title = PET Quantification of 5-HT_2A Receptors in the Human Brain: A Constant Infusion Paradigm with [¹⁸F] Altanserin
journal = The Journal of Nuclear Medicine
volume = 41
issue = 2
pages = 234&ndash;241
url = http://jnm.snmjournals.org/cgi/content/abstract/41/2/234
pmid = 10688105] or bolus-infusion [Cite journal
author = Lars H Pinborg, Karen H Adams, Claus Svarer, Søren Holm*, Steen G Hasselbalch, Steven Haugbøl, Jacob Madsen and Gitte M Knudsen
title = Quantification of 5-HT_2A Receptors in the Human Brain Using ¹⁸FAltanserin-PET and the Bolus/Infusion Approach
journal = Journal of Cerebral Blood Flow & Metabolism
year = 2003
volume = 23
pages = 985&ndash;996
doi = 10.1097/01.WCB.0000074092.59115.23
url = http://www.nature.com/jcbfm/journal/v23/n8/abs/9591447a.html] delivery of altanserin. Other studies have compared altanserin binding to subject variables such as age, personality trait and neuropsychiatric disorder.

The altanserin PET scan shows high binding in neocortex.The cerebellum is often regarded as a region with no specific 5-HT_2A binding and the brain region is used as a reference in some studies, even though an autoradiography study has found nonnegligible levels of 5-HT_2A binding in the human cerebellum, [Cite journal
author = Sharon L. Eastwood, Philip W. J. Burnet, Rebecca Gittins, Kate Baker, Paul J. Harrison
title = Expression of serotonin 5-HT_2A receptors in the human cerebellum and alterations in schizophrenia
journal = Synapse
volume = 42
issue = 2
pages = 104&ndash;114
month = November
year = 2001
doi = 10.1002/syn.1106] and another type of study have observed strong immunoreaction against 5-HT_2A receptor protein in rat Purkinje cells. [Cite journal
author = Toru Maeshima, Fumihiro Shutoh, Shun Hamada, Kouji Senzaki, Kayoko Hamaguchi-Hamada, Ryuzo Ito, Nobuo Okado
title = Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells
journal = Neuroscience Letters
year = 1998
month = August
volume = 252
number = 1
pages = 72&ndash;74
pmid = 9756362
doi = 10.1016/S0304-3940(98)00546-1 ]

In the table below is an overview of the results of altanserin binding seen in human PET-studies.A consistent finding across altanserin studies has been that the binding decreases with age.This is in line with "in vitro" studies of the 5-HT_2A receptor, [Cite journal
author = Jan O. Marcusson, David G. Morgan, Bengt Winblad, Caleb E. Finch
title = Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age
journal = Brain Research
year = 1984
month = October
volume = 311
issue = 1
pages = 51&ndash;56
pmid = 6488044
doi = 10.1016/0006-8993(84)91397-0 ] as well as PET studies with other radioligands that binds to the receptor. [Cite journal
author = D. F. Wong, H. N. Wagner Jr, R. F. Dannals, J. M. Links, J. J. Frost, H. T. Ravert, A. A. Wilson, A. E. Rosenbaum, Albert Gjedde, K. H. Douglass, "et al."
title = Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain
journal = Science
month = December
year = 1984
volume = 226
issue = 4681
pages = 1393&ndash;1396
doi = 10.1126/science.6334363
url = http://www.sciencemag.org/cgi/content/abstract/226/4681/1393]

The result for recovered bulimia-type anorexia nervosaCite journal
author = Ursula F. Bailer, Julie C. Price, Carolyn C. Meltzer, Chester A. Mathis, Guido K. Frank, Lisa Weissfeld, Claire W. McConaha, Shannan E. Henry, Sarah Brooks-Achenbach, Nicole C. Barbarich, and Walter H. Kaye
title = Altered 5-HT_2A receptor binding after recovery from bulimia-type anorexia nervosa: Relationships to harm avoidance and drive for thinness.
journal = Neuropsychopharmacology
year = 2004
volume = 29
pages = 1143&ndash;1155
url = http://www.medical-tribune.at/mm/Bailer_NPP20046.pdf
doi = 10.1038/sj.npp.1300430] is in line with a SPECT study of anorexia nervosa patients, that found a decrease in frontal, occipital and parietal cortices.The results of PET studies of the 5-HT_2A in depression has been mixed. [Cite journal
author = Masahiro Fujita, Dennis S. Charneya, c and Robert B. Innis
title = Imaging serotonergic neurotransmission in depression: hippocampal pathophysiology may mirror global brain alterations
journal = Biological Psychiatry
volume = 48
issue = 8
month = October
year = 2000
pages = 801&ndash;812
doi = 10.1016/S0006-3223(00)00960-4 ]

Altanserin binding has also been examine in twins, where one study showed higher correlation between monozygotic twin pairs than between dizygotic twin pairs, giving evidence that the binding is "strongly genetically determined". [Cite journal
author = Lars H. Pinborg, Haroon Arfan, Steven Haugbol, Kirsten Ohm Kyvik, Jacob V. B. Hjelmborg, Claus Svarer, Vibe G. Frokjaer, Olaf B. Paulson, Soren Holm & Gitte M. Knudsen
title = The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined
journal = NeuroImage
volume = 40
issue = 3
pages = 1175–1170
year = 2008
month = April
doi = 10.1016/j.neuroimage.2007.09.019
pmid = 18291676]

References