Altanserin

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Altanserin
File:Altanserin.png
Systematic (IUPAC) name
3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one
Identifiers
CAS Number 76330-71-7
ATC code none
PubChem CID 3033677
ChemSpider 2298299
Chemical data
Formula C22H22FN3O2S
Molar mass 411.49[1][[Script error: No such module "String".]]
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Altanserin is a compound that binds to the 5-HT2A receptor (serotonin 2A receptor). It is a yellowish solid.[1] 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.[2][3]

An alternative for PET imaging the 5-HT2A receptor is the [11C]MDL 100,907 radioligand. Fluorine-18-altanserin and tritium-MDL 100,907 have shown very comparable binding.[4] Both altanserin and MDL 100,907 are 5-HT2A receptor antagonists.[4] [18F]-setoperone can also be used in PET.

An alternative SPECT radioligand is the [123I]-5-I-R91150 receptor antagonist.[5]

A rapid chemical synthesis of fluorine-18 and H-2 dual-labeled altanserin has been described.[6]

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

File:ECAT-Exact-HR--PET-Scanner.jpg
A PET scanner. Human experiments with fluorine-18 altanserin are performed in these types of brain scanners.

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 1990s.[7][8] Some of these studies have considered methodogical issues such as the reproducibility of the method[9][10] or whether to use constant infusion[11] or bolus-infusion[12] 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-HT2A binding and the brain region is used as a reference in some studies, even though an autoradiography study has found nonnegligible levels of 5-HT2A binding in the human cerebellum,[13] and another type of study have observed strong immunoreaction against 5-HT2A receptor protein in rat Purkinje cells.[14]

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-HT2A receptor,[15] as well as PET studies with other radioligands that binds to the receptor.[16]

The result for recovered bulimia-type anorexia nervosa[17] is in line with a SPECT study of anorexia nervosa patients, that found a decrease in frontal, occipital and parietal cortices.[5] The results of PET studies of the 5-HT2A in depression has been mixed.[18]

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".[19]

Altanserin neuroimaging studies
What Result Reference
Sex Higher binding in men [20]
Body mass index Correlation in cortex [21]
Neuroticism (NEO PI-R) Increase in frontolimbic region [22]
Tourette syndrome Increase [23]
Obsessive-compulsive disorder Increase in caudate nuclei [24]
(Recovered) bulimia-type anorexia nervosa Decrease in left subgenual cingulate, left parietal cortex and right occipital cortex [17]
Unipolar depression Decrease in a region in right hemisphere (posterolateral orbitofrontal cortex and the anterior insular cortex) [25]
Major depressive disorder Decrease in hippocampus [26]
Older depressed patients Decrease in hippocampus [27]
Borderline personality disorder Increase in hippocampus [28]
Schizophrenia No significant cortical difference, higher binding in caudate [29]
At-risk mental state Decrease [30] See also [31]
Age Decrease [32]
Age Decrease [33]
Age Decrease in cortical regions (except occipital), increase in cerebellum [34]
Mild cognitive impairment Decrease [35]
Alzheimer's disease Decrease in amygdalo-hippocampal complex and cortical regions, such as anterior cingulate, lateral temporal cortex, prefrontal cortex and sensorimotor cortex [36]

References

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  1. ↑ 1.0 1.1 ABX, Altanserin, Radeberg, Germany.
  2. ↑ Christian Lemaire, R. Cantineau, M. Guillaume, A. Plenevaux, Leon Christiaens (December 1, 1991). "Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats". Journal of Nuclear Medicine. 32 (12): 2266–2277. PMID 1744713. 
  3. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  5. ↑ 5.0 5.1 Kurt Audenaert, Koen Van Laere, Filip Dumont, Miriam Vervaet, Ingeborg Goethals, Guido Slegers, John Mertens, Cees van Heeringen, Rudi A. Dierckx. "Decreased 5-HT2A Receptor Binding in Patients with Anorexia Nervosa". Journal of Nuclear Medicine. 44: 163–169. 
  6. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  7. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  8. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  9. ↑ 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 (1998). "Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain". Synapse. 30 (4): 380–392. doi:10.1002/(SICI)1098-2396(199812)30:4<380::AID-SYN5>3.0.CO;2-U. 
  10. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  11. ↑ 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 (February 1, 2000). "PET Quantification of 5-HT2A Receptors in the Human Brain: A Constant Infusion Paradigm with [18F]Altanserin". The Journal of Nuclear Medicine. 41 (2): 234–241. PMID 10688105. 
  12. ↑ Lars H Pinborg, Karen H Adams, Claus Svarer, Søren Holm*, Steen G Hasselbalch, Steven Haugbøl, Jacob Madsen and Gitte M Knudsen (2003). "Quantification of 5-HT2A Receptors in the Human Brain Using [18F]Altanserin-PET and the Bolus/Infusion Approach". Journal of Cerebral Blood Flow & Metabolism. 23 (8): 985–996. doi:10.1097/01.WCB.0000074092.59115.23. PMID 12902843. 
  13. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  15. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  16. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  17. ↑ 17.0 17.1 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 (2004). "Altered 5-HT2A receptor binding after recovery from bulimia-type anorexia nervosa: Relationships to harm avoidance and drive for thinness" (PDF). Neuropsychopharmacology. 29 (6): 1143–1155. doi:10.1038/sj.npp.1300430. PMID 15054474. 
  18. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  19. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  20. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  21. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  22. ↑ Vibe G. Frøkjær, Erik Lykke Mortensen, Finn Årup Nielsen, Steven Haugbøl, Lars H Pinborg, Karen H. Adams, Claus Svarer, Steen G. Hasselbalch, Søren Holm, Olaf B. Paulson, Gitte Moos Knudsen (2008). "Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder". Biological Psychiatry. 63 (6): 569. doi:10.1016/j.biopsych.2007.07.009. PMID 17884017. 
  23. ↑ Steven Haugbøl, Lars H. Pinborg, Lisbeth Regeur, Elsebet S. Hansen, Tom G. Bolwig, Finn Årup Nielsen, Claus Svarer, Lene T. Skovgaardand Gitte M. Knudsen (2008). "Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome". The International Journal of Neuropsychopharmacology. 63 (2): 569. doi:10.1017/S1461145706006559. PMID 16945163. 
  24. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  25. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  26. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  27. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  28. ↑ P. Soloff, J. Price, C. Meltzer, A. Fabio, G. Frank, W. Kaye (2007). "5HT2A Receptor Binding is Increased in Borderline Personality Disorder". Biological Psychiatry. 62 (6): 580–587. doi:10.1016/j.biopsych.2006.10.022. PMID 17448449. 
  29. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. Electronic publication ahead of print
  30. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  31. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  32. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  33. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  34. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  35. ↑ Hasselbalch SG, Madsen K, Svarer C, Pinborg LH, Holm S, Olaf B. Paulson, Waldemar G, Gitte Moos Knudsen (2007). "Reduced 5-HT2A receptor binding in patients with mild cognitive impairment". Neurobiology of Aging. 29 (12): 1830. doi:10.1016/j.neurobiolaging.2007.04.011. PMID 17544547. 
  36. ↑ Carolyn Cidis Meltzer, Julie C. Price, Chester A. Mathis, Phil J. Greer, Michael N. Cantwell, Patricia R. Houck, Benoit H. Mulsant, Doron Ben-Eliezer, Brian Lopresti, Steven T. DeKosky, and Charles F. Reynolds, III (December 1, 1999). "PET Imaging of Serotonin Type 2A Receptors in Late-Life Neuropsychiatric Disorders". The American Journal of Psychiatry. 156 (12): 1871–1878. PMID 10588399. 
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