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In preclinical studies it had been found to bind to soluble [[amyloid beta]] and inhibit the formation of neurotoxic aggregates.<ref name=AD2012rev/><ref name="pmid17908052">{{cite journal | vauthors = Aisen PS, Gauthier S, Vellas B, Briand R, Saumier D, Laurin J, Garceau D | title = Alzhemed: a potential treatment for Alzheimer's disease | journal = Current Alzheimer Research | volume = 4 | issue = 4 | pages = 473–8 | year = 2007 | pmid = 17908052 | doi = 10.2174/156720507781788882 }}</ref> Homotaurine has also shown [[anticonvulsant]] activities, reduction in skeletal [[muscle tonus]], and [[hypothermic]] activity.<ref name=Metabolism2013/>
In preclinical studies it had been found to bind to soluble [[amyloid beta]] and inhibit the formation of neurotoxic aggregates.<ref name=AD2012rev/><ref name="pmid17908052">{{cite journal | vauthors = Aisen PS, Gauthier S, Vellas B, Briand R, Saumier D, Laurin J, Garceau D | title = Alzhemed: a potential treatment for Alzheimer's disease | journal = Current Alzheimer Research | volume = 4 | issue = 4 | pages = 473–8 | year = 2007 | pmid = 17908052 | doi = 10.2174/156720507781788882 }}</ref> Homotaurine has also shown [[anticonvulsant]] activities, reduction in skeletal [[muscle tonus]], and [[hypothermic]] activity.<ref name=Metabolism2013/>


Homotaurine has been reported as a [[GABA]] antagonist<ref name=OrgChem2007/> as well as a GABA agonist.<ref name=Metabolism2013>Oja SS and Kontro P. Taurine. Chapter 18 in Metabolism in the Nervous System, Ed. Lajtha ANS. Springer Science & Business Media, 2013. {{ISBN|9781468443677}}. [https://books.google.es/books?id=du_TBwAAQBAJ&pg=PA520 Page 520]</ref><ref name=PharmPrinc2011>Armen H. Tashjian and Ehrin J. Armstrong. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Edited by David E. Golan. Lippincott Williams & Wilkins, 2011 {{ISBN|9781451118056}}. [https://books.google.com/books?id=kjCCMZHInigC&pg=PA308 Page 308]</ref> In vitro studies have found that homotaurine is a [[GABAA receptor|GABA<sub>A</sub>]] partial agonist<ref>{{cite journal|title=Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.|pmid=25119985|author=Reyes-Haro D1, Cabrera-Ruíz E, Estrada-Mondragón A, Miledi R, Martínez-Torres A. | doi=10.1007/s00726-014-1813-0|volume=46|year=2014|journal=Amino Acids|pages=2587–93}}</ref> as well as a [[GABAB receptor|GABA<sub>B</sub>]] receptor partial agonist with low efficacy, becoming an antagonist and a displacing full agonist of [[Gamma-Aminobutyric acid|GABA]] or [[baclofen]] at this receptor.<ref>{{cite journal|title=Homotaurine: a GABAB antagonist in guinea-pig ileum.|pmid=6652358|vauthors=Giotti A, Luzzi S, Spagnesi S, Zilletti L | volume=79|pmc=2044932|year=1983|journal=Br. J. Pharmacol.|pages=855–62|doi=10.1111/j.1476-5381.1983.tb10529.x}}</ref> In a study in rats, homotaurine reversed the [[catatonia]] induced by [[baclofen]] (the prototypical [[GABAB receptor|GABA<sub>B</sub>]] agonist),<ref>{{cite journal|title=Baclofen induces catatonia in rats.|pmid=2823166|author=Mehta AK1, Ticku MK. | volume=26|year=1987|journal=Neuropharmacology|pages=1419–23|doi=10.1016/0028-3908(87)90108-0}}</ref> and was able to produce analgesia via the [[GABAB receptor|GABA<sub>B</sub>]] receptor, an effect that was abolished when CGP 35348, a [[GABAB receptor|GABA<sub>B</sub>]] receptor antagonist was applied.<ref>{{cite journal|title=GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.|pmid=9510095|author=Serrano MI1, Serrano JS, Fernández A, Asadi I, Serrano-Martino MC. | volume=30|year=1998|journal=Gen. Pharmacol.|pages=411–5|doi=10.1016/s0306-3623(97)00279-6}}</ref><ref>{{cite journal|title=Role of K+ -channels in homotaurine-induced analgesia.|pmid=11468027|author=Serrano MI1, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. | volume=15|year=2001|journal=Fundam Clin Pharmacol|pages=167–73|doi=10.1046/j.1472-8206.2001.00026.x}}</ref>
Homotaurine has been reported as a [[GABA]] antagonist<ref name=OrgChem2007/> as well as a GABA agonist.<ref name=Metabolism2013>Oja SS and Kontro P. Taurine. Chapter 18 in Metabolism in the Nervous System, Ed. Lajtha ANS. Springer Science & Business Media, 2013. {{ISBN|9781468443677}}. [https://books.google.es/books?id=du_TBwAAQBAJ&pg=PA520 Page 520]</ref><ref name=PharmPrinc2011>Armen H. Tashjian and Ehrin J. Armstrong. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Edited by David E. Golan. Lippincott Williams & Wilkins, 2011 {{ISBN|9781451118056}}. [https://books.google.com/books?id=kjCCMZHInigC&pg=PA308 Page 308]</ref> In vitro studies have found that homotaurine is a [[GABAA receptor|GABA<sub>A</sub>]] partial agonist<ref>{{cite journal|title=Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.|pmid=25119985|author=Reyes-Haro D1, Cabrera-Ruíz E, Estrada-Mondragón A, Miledi R, Martínez-Torres A. | doi=10.1007/s00726-014-1813-0|volume=46|issue=11|year=2014|journal=Amino Acids|pages=2587–93}}</ref> as well as a [[GABAB receptor|GABA<sub>B</sub>]] receptor partial agonist with low efficacy, becoming an antagonist and a displacing full agonist of [[Gamma-Aminobutyric acid|GABA]] or [[baclofen]] at this receptor.<ref>{{cite journal|title=Homotaurine: a GABAB antagonist in guinea-pig ileum.|pmid=6652358|vauthors=Giotti A, Luzzi S, Spagnesi S, Zilletti L | volume=79|issue=4|pmc=2044932|year=1983|journal=Br. J. Pharmacol.|pages=855–62|doi=10.1111/j.1476-5381.1983.tb10529.x}}</ref> In a study in rats, homotaurine reversed the [[catatonia]] induced by [[baclofen]] (the prototypical [[GABAB receptor|GABA<sub>B</sub>]] agonist),<ref>{{cite journal|title=Baclofen induces catatonia in rats.|pmid=2823166|author=Mehta AK1, Ticku MK. | volume=26|issue=9|year=1987|journal=Neuropharmacology|pages=1419–23|doi=10.1016/0028-3908(87)90108-0}}</ref> and was able to produce analgesia via the [[GABAB receptor|GABA<sub>B</sub>]] receptor, an effect that was abolished when CGP 35348, a [[GABAB receptor|GABA<sub>B</sub>]] receptor antagonist was applied.<ref>{{cite journal|title=GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.|pmid=9510095|author=Serrano MI1, Serrano JS, Fernández A, Asadi I, Serrano-Martino MC. | volume=30|issue=3|year=1998|journal=Gen. Pharmacol.|pages=411–5|doi=10.1016/s0306-3623(97)00279-6}}</ref><ref>{{cite journal|title=Role of K+ -channels in homotaurine-induced analgesia.|pmid=11468027|author=Serrano MI1, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. | volume=15|issue=3|year=2001|journal=Fundam Clin Pharmacol|pages=167–73|doi=10.1046/j.1472-8206.2001.00026.x}}</ref>


One study in rats showed that homotaurine suppressed ethanol-stimulated dopamine release, as well as ethanol intake and preference in rats in a way similar to the ''N''-acetyl [[derivative (chemistry)|derivative]] of homotaurine, [[acamprosate]].<ref>{{cite journal|title=Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.|pmid=11864639|vauthors=Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW | volume=437|year=2002|journal=Eur. J. Pharmacol.|pages=55–61|doi=10.1016/s0014-2999(02)01272-4}}</ref> Acamprosate was approved by the FDA in 2004 to treat alcohol dependence.<ref name=OrgChem2007>{{cite book | last1 = Lednicer | first1 = Daniel | name-list-format = vanc | title = The Organic Chemistry of Drug Synthesis | date = 2008 | publisher = John Wiley & Sons | location = Hoboken | isbn = 978-0-470-18066-2 | edition = 7th | url = https://books.google.com/books?id=N6OAhuiHqiIC&pg=PA15 | page = 15 }}</ref>
One study in rats showed that homotaurine suppressed ethanol-stimulated dopamine release, as well as ethanol intake and preference in rats in a way similar to the ''N''-acetyl [[derivative (chemistry)|derivative]] of homotaurine, [[acamprosate]].<ref>{{cite journal|title=Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.|pmid=11864639|vauthors=Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW | volume=437|issue=1–2|year=2002|journal=Eur. J. Pharmacol.|pages=55–61|doi=10.1016/s0014-2999(02)01272-4}}</ref> Acamprosate was approved by the FDA in 2004 to treat alcohol dependence.<ref name=OrgChem2007>{{cite book | last1 = Lednicer | first1 = Daniel | name-list-format = vanc | title = The Organic Chemistry of Drug Synthesis | date = 2008 | publisher = John Wiley & Sons | location = Hoboken | isbn = 978-0-470-18066-2 | edition = 7th | url = https://books.google.com/books?id=N6OAhuiHqiIC&pg=PA15 | page = 15 }}</ref>


==See also==
==See also==

Revision as of 14:18, 20 September 2018

Homotaurine[1]
Skeletal formula
Ball-and-stick model
Names
IUPAC name
3-Aminopropane-1-sulfonic acid
Other names
Tramiprosate; Alzhemed; 3-APS
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.020.889 Edit this at Wikidata
KEGG
  • InChI=1S/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7) checkY
    Key: SNKZJIOFVMKAOJ-UHFFFAOYSA-N checkY
  • InChI=1/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7)
    Key: SNKZJIOFVMKAOJ-UHFFFAOYAT
  • O=S(=O)(O)CCCN
Properties
C3H9NO3S
Molar mass 139.17 g·mol−1
Melting point 293 °C (559 °F; 566 K) (decomposition)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Homotaurine (also known as tramiprosate (INN), 3-amino-1-propanesulfonic acid, or 3-APS) is a synthetic organic compound. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.[2]

Homotaurine was investigated in a Phase III clinical trial as a potential treatment for Alzheimer's disease that did not show efficacy in its primary endpoints.[3]

Biochemical properties

In preclinical studies it had been found to bind to soluble amyloid beta and inhibit the formation of neurotoxic aggregates.[3][4] Homotaurine has also shown anticonvulsant activities, reduction in skeletal muscle tonus, and hypothermic activity.[5]

Homotaurine has been reported as a GABA antagonist[2] as well as a GABA agonist.[5][6] In vitro studies have found that homotaurine is a GABAA partial agonist[7] as well as a GABAB receptor partial agonist with low efficacy, becoming an antagonist and a displacing full agonist of GABA or baclofen at this receptor.[8] In a study in rats, homotaurine reversed the catatonia induced by baclofen (the prototypical GABAB agonist),[9] and was able to produce analgesia via the GABAB receptor, an effect that was abolished when CGP 35348, a GABAB receptor antagonist was applied.[10][11]

One study in rats showed that homotaurine suppressed ethanol-stimulated dopamine release, as well as ethanol intake and preference in rats in a way similar to the N-acetyl derivative of homotaurine, acamprosate.[12] Acamprosate was approved by the FDA in 2004 to treat alcohol dependence.[2]

See also

References

  1. ^ Homotaurine at Sigma-Aldrich
  2. ^ a b c Lednicer, Daniel (2008). The Organic Chemistry of Drug Synthesis (7th ed.). Hoboken: John Wiley & Sons. p. 15. ISBN 978-0-470-18066-2. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  3. ^ a b Caltagirone C; et al. (Dec 2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review". Aging Clin Exp Res. 24 (6): 580–7. doi:10.3275/8585. PMID 22961121. {{cite journal}}: Explicit use of et al. in: |author= (help)
  4. ^ Aisen PS, Gauthier S, Vellas B, Briand R, Saumier D, Laurin J, Garceau D (2007). "Alzhemed: a potential treatment for Alzheimer's disease". Current Alzheimer Research. 4 (4): 473–8. doi:10.2174/156720507781788882. PMID 17908052.
  5. ^ a b Oja SS and Kontro P. Taurine. Chapter 18 in Metabolism in the Nervous System, Ed. Lajtha ANS. Springer Science & Business Media, 2013. ISBN 9781468443677. Page 520
  6. ^ Armen H. Tashjian and Ehrin J. Armstrong. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Edited by David E. Golan. Lippincott Williams & Wilkins, 2011 ISBN 9781451118056. Page 308
  7. ^ Reyes-Haro D1, Cabrera-Ruíz E, Estrada-Mondragón A, Miledi R, Martínez-Torres A. (2014). "Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs". Amino Acids. 46 (11): 2587–93. doi:10.1007/s00726-014-1813-0. PMID 25119985.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  8. ^ Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983). "Homotaurine: a GABAB antagonist in guinea-pig ileum". Br. J. Pharmacol. 79 (4): 855–62. doi:10.1111/j.1476-5381.1983.tb10529.x. PMC 2044932. PMID 6652358.
  9. ^ Mehta AK1, Ticku MK. (1987). "Baclofen induces catatonia in rats". Neuropharmacology. 26 (9): 1419–23. doi:10.1016/0028-3908(87)90108-0. PMID 2823166.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  10. ^ Serrano MI1, Serrano JS, Fernández A, Asadi I, Serrano-Martino MC. (1998). "GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia". Gen. Pharmacol. 30 (3): 411–5. doi:10.1016/s0306-3623(97)00279-6. PMID 9510095.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  11. ^ Serrano MI1, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. (2001). "Role of K+ -channels in homotaurine-induced analgesia". Fundam Clin Pharmacol. 15 (3): 167–73. doi:10.1046/j.1472-8206.2001.00026.x. PMID 11468027.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  12. ^ Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW (2002). "Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release". Eur. J. Pharmacol. 437 (1–2): 55–61. doi:10.1016/s0014-2999(02)01272-4. PMID 11864639.
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