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'''Homotaurine''' (also known as '''tramiprosate''' ([[International Nonproprietary Name|INN]]), '''3-amino-1-propanesulfonic acid''', or '''3-APS''') is a natural amino acid found in seaweed.<ref>{{cite journal | pmc = 4172065| year = 2014| last1 = Martorana| first1 = A.| title = Homotaurine Induces Measurable Changes of Short Latency Afferent Inhibition in a Group of Mild Cognitive Impairment Individuals| journal = Frontiers in Aging Neuroscience| volume = 6| pages = 254| last2 = Di Lorenzo| first2 = F.| last3 = Manenti| first3 = G.| last4 = Semprini| first4 = R.| last5 = Koch| first5 = G.| pmid = 25295005| doi = 10.3389/fnagi.2014.00254}}</ref> It is analogous to [[taurine]], but with an extra carbon in its chain. It has [[GABAergic]] activity, apparently by mimicking GABA, which it resembles.<ref name=OrgChem2007/>
'''Homotaurine''' (also known as '''tramiprosate''' ([[International Nonproprietary Name|INN]]), '''3-amino-1-propanesulfonic acid''', or '''3-APS''') is a natural amino acid found in seaweed.<ref>{{cite journal | pmc = 4172065| year = 2014| last1 = Martorana| first1 = A.| title = Homotaurine Induces Measurable Changes of Short Latency Afferent Inhibition in a Group of Mild Cognitive Impairment Individuals| journal = Frontiers in Aging Neuroscience| volume = 6| pages = 254| last2 = Di Lorenzo| first2 = F.| last3 = Manenti| first3 = G.| last4 = Semprini| first4 = R.| last5 = Koch| first5 = G.| pmid = 25295005| doi = 10.3389/fnagi.2014.00254}}</ref> It is analogous to [[taurine]], but with an extra carbon in its chain. It has [[GABAergic]] activity, apparently by mimicking GABA, which it resembles.<ref name=OrgChem2007/>


Homotaurine was investigated in a [[Phase III clinical trials|Phase III]] clinical trial as a potential treatment for [[Alzheimer's disease]] that did not show efficacy.<ref name=AD2012rev>{{cite journal | doi = 10.3275/8585 | pmid = 22961121 | year = 2012 | last1 = Caltagirone | first1 = C. | title = The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: A review | journal = Aging Clinical and Experimental Research | volume = 24 | issue = 6 | pages = 580–7 | last2 = Ferrannini | first2 = L. | last3 = Marchionni | first3 = N. | last4 = Nappi | first4 = G. | last5 = Scapagnini | first5 = G. | last6 = Trabucchi | first6 = M. }}</ref> A study in cognitive impairment done in 2018 did show positive benefits.<ref>http://www.jgerontology-geriatrics.com/wp-content/uploads/2018/03/03_Martorana-1.pdf</ref>
Homotaurine was investigated in a [[Phase III clinical trials|Phase III]] clinical trial as a potential treatment for [[Alzheimer's disease]] that did not show efficacy.<ref name=AD2012rev>{{cite journal | doi = 10.3275/8585 | pmid = 22961121 | year = 2012 | last1 = Caltagirone | first1 = C. | title = The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: A review | journal = Aging Clinical and Experimental Research | volume = 24 | issue = 6 | pages = 580–7 | last2 = Ferrannini | first2 = L. | last3 = Marchionni | first3 = N. | last4 = Nappi | first4 = G. | last5 = Scapagnini | first5 = G. | last6 = Trabucchi | first6 = M. | s2cid = 10816430 }}</ref> A study in cognitive impairment done in 2018 did show positive benefits.<ref>http://www.jgerontology-geriatrics.com/wp-content/uploads/2018/03/03_Martorana-1.pdf</ref>


==Biochemical properties==
==Biochemical properties==
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 | doi = 10.2174/156720507781788882 | pmid = 17908052 | title = Alzhemed: A Potential Treatment for Alzheimers Disease | journal = Current Alzheimer Research | volume = 4 | issue = 4 | pages = 473–478 | year = 2007 | last1 = Aisen | first1 = Paul | last2 = Gauthier | first2 = Serge | last3 = Vellas | first3 = Bruno | last4 = Briand | first4 = Richard | last5 = Saumier | first5 = Daniel | last6 = Laurin | first6 = Julie | last7 = Garceau | first7 = Denis }}</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 | doi = 10.2174/156720507781788882 | pmid = 17908052 | title = Alzhemed: A Potential Treatment for Alzheimers Disease | journal = Current Alzheimer Research | volume = 4 | issue = 4 | pages = 473–478 | year = 2007 | last1 = Aisen | first1 = Paul | last2 = Gauthier | first2 = Serge | last3 = Vellas | first3 = Bruno | last4 = Briand | first4 = Richard | last5 = Saumier | first5 = Daniel | last6 = Laurin | first6 = Julie | last7 = Garceau | first7 = Denis }}</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>{{cite book | author = Oja SS and Kontro P. | title = Chapter 18: Taurine | work = Metabolism in the Nervous System | editor = Lajtha ANS | publisher = Springer Science & Business Media| date = 2013 | url = https://books.google.com/books?id=du_TBwAAQBAJ&pg=PA520 | page = 520 | isbn = 9781468443677}}</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 | doi =10.1007/s00726-014-1813-0 | pmid =25119985 | title =Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs | journal =Amino Acids | volume =46 | issue =11 | pages =2587–2593 | year =2014 | last1 =Reyes-Haro | first1 =Daniel | last2 =Cabrera-Ruíz | first2 =Elizabeth | last3 =Estrada-Mondragón | first3 =Argel | last4 =Miledi | first4 =Ricardo | last5 =Martínez-Torres | first5 =Ataúlfo }}</ref> as well as a [[GABAB receptor|GABA<sub>B</sub>]] receptor partial agonist with low efficacy, becoming an antagonist and displacing the full agonists GABA and [[baclofen]] at this receptor.<ref>{{cite journal | doi = 10.1111/j.1476-5381.1983.tb10529.x | title = Homotaurine: A GABAB antagonist in guinea-pig ileum | journal = British Journal of Pharmacology | volume = 79 | issue = 4 | pages = 855–862 | year = 1983 | last1 = Giotti | first1 = A. | last2 = Luzzi | first2 = S. | last3 = Spagnesi | first3 = S. | last4 = Zilletti | first4 = Lucilla | pmc = 2044932 | pmid=6652358}}</ref> In a study in rats, homotaurine reversed the [[catatonia]] induced by [[baclofen]] (the prototypical GABA<sub>B</sub> agonist),<ref>{{cite journal | doi = 10.1016/0028-3908(87)90108-0| title = Baclofen induces catatonia in rats| journal = Neuropharmacology| volume = 26| issue = 9| pages = 1419–1423| year = 1987| last1 = Mehta| first1 = A.| last2 = Ticku| first2 = M.}}</ref> and was able to produce analgesia via the GABA<sub>B</sub> receptor, an effect that was abolished when [[CGP-35348]], a GABA<sub>B</sub> receptor antagonist was applied.<ref>{{cite journal | doi =10.1016/s0306-3623(97)00279-6| title =GABAB Receptors and Opioid Mechanisms Involved in Homotaurine-Induced Analgesia| journal =General Pharmacology: The Vascular System| volume =30| issue =3| pages =411–415| year =1998| last1 =Serrano| first1 =M.Isabel| last2 =Serrano| first2 =Jose S.| last3 =Fernández| first3 =Ana| last4 =Asadi| first4 =Ihklas| last5 =Serrano-Martino| first5 =M.Carmen}}</ref><ref>{{cite journal | doi = 10.1046/j.1472-8206.2001.00026.x| title = Role of K+-channels in homotaurine-induced analgesia| journal = Fundamental and Clinical Pharmacology| volume = 15| issue = 3| pages = 167–173| year = 2001| last1 = Serrano| first1 = Maria Isabel| last2 = Serrano| first2 = Jose S.| last3 = Asadi| first3 = Ikhlas| last4 = Fernandez| first4 = Ana| last5 = Serrano-Martino| first5 = Maria Carmen}}</ref>
Homotaurine has been reported as a [[GABA]] antagonist,<ref name=OrgChem2007/> as well as a GABA agonist.<ref name=Metabolism2013>{{cite book | author = Oja SS and Kontro P. | title = Chapter 18: Taurine | work = Metabolism in the Nervous System | editor = Lajtha ANS | publisher = Springer Science & Business Media| date = 2013 | url = https://books.google.com/books?id=du_TBwAAQBAJ&pg=PA520 | page = 520 | isbn = 9781468443677}}</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 | doi =10.1007/s00726-014-1813-0 | pmid =25119985 | title =Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs | journal =Amino Acids | volume =46 | issue =11 | pages =2587–2593 | year =2014 | last1 =Reyes-Haro | first1 =Daniel | last2 =Cabrera-Ruíz | first2 =Elizabeth | last3 =Estrada-Mondragón | first3 =Argel | last4 =Miledi | first4 =Ricardo | last5 =Martínez-Torres | first5 =Ataúlfo | s2cid =10319072 }}</ref> as well as a [[GABAB receptor|GABA<sub>B</sub>]] receptor partial agonist with low efficacy, becoming an antagonist and displacing the full agonists GABA and [[baclofen]] at this receptor.<ref>{{cite journal | doi = 10.1111/j.1476-5381.1983.tb10529.x | title = Homotaurine: A GABAB antagonist in guinea-pig ileum | journal = British Journal of Pharmacology | volume = 79 | issue = 4 | pages = 855–862 | year = 1983 | last1 = Giotti | first1 = A. | last2 = Luzzi | first2 = S. | last3 = Spagnesi | first3 = S. | last4 = Zilletti | first4 = Lucilla | pmc = 2044932 | pmid=6652358}}</ref> In a study in rats, homotaurine reversed the [[catatonia]] induced by [[baclofen]] (the prototypical GABA<sub>B</sub> agonist),<ref>{{cite journal | doi = 10.1016/0028-3908(87)90108-0| title = Baclofen induces catatonia in rats| journal = Neuropharmacology| volume = 26| issue = 9| pages = 1419–1423| year = 1987| last1 = Mehta| first1 = A.| last2 = Ticku| first2 = M.| pmid = 2823166| s2cid = 24010833}}</ref> and was able to produce analgesia via the GABA<sub>B</sub> receptor, an effect that was abolished when [[CGP-35348]], a GABA<sub>B</sub> receptor antagonist was applied.<ref>{{cite journal | doi =10.1016/s0306-3623(97)00279-6| title =GABAB Receptors and Opioid Mechanisms Involved in Homotaurine-Induced Analgesia| journal =General Pharmacology: The Vascular System| volume =30| issue =3| pages =411–415| year =1998| last1 =Serrano| first1 =M.Isabel| last2 =Serrano| first2 =Jose S.| last3 =Fernández| first3 =Ana| last4 =Asadi| first4 =Ihklas| last5 =Serrano-Martino| first5 =M.Carmen| pmid =9510095}}</ref><ref>{{cite journal | doi = 10.1046/j.1472-8206.2001.00026.x| title = Role of K+-channels in homotaurine-induced analgesia| journal = Fundamental and Clinical Pharmacology| volume = 15| issue = 3| pages = 167–173| year = 2001| last1 = Serrano| first1 = Maria Isabel| last2 = Serrano| first2 = Jose S.| last3 = Asadi| first3 = Ikhlas| last4 = Fernandez| first4 = Ana| last5 = Serrano-Martino| first5 = Maria Carmen| pmid = 11468027}}</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 | doi = 10.1016/s0014-2999(02)01272-4| pmid = 11864639| title = Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release| journal = European Journal of Pharmacology| volume = 437| issue = 1–2| pages = 55–61| year = 2002| last1 = Olive| first1 = M.Foster| last2 = Nannini| first2 = Michelle A.| last3 = Ou| first3 = Christine J.| last4 = Koenig| first4 = Heather N.| last5 = Hodge| first5 = Clyde W.}}</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 | doi = 10.1016/s0014-2999(02)01272-4| pmid = 11864639| title = Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release| journal = European Journal of Pharmacology| volume = 437| issue = 1–2| pages = 55–61| year = 2002| last1 = Olive| first1 = M.Foster| last2 = Nannini| first2 = Michelle A.| last3 = Ou| first3 = Christine J.| last4 = Koenig| first4 = Heather N.| last5 = Hodge| first5 = Clyde W.}}</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>

Revision as of 05:59, 15 September 2020

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
UNII
  • 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 natural amino acid found in seaweed.[2] It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.[3]

Homotaurine was investigated in a Phase III clinical trial as a potential treatment for Alzheimer's disease that did not show efficacy.[4] A study in cognitive impairment done in 2018 did show positive benefits.[5]

Biochemical properties

In preclinical studies it had been found to bind to soluble amyloid beta and inhibit the formation of neurotoxic aggregates.[4][6] Homotaurine has also shown anticonvulsant activities, reduction in skeletal muscle tonus, and hypothermic activity.[7]

Homotaurine has been reported as a GABA antagonist,[3] as well as a GABA agonist.[7][8] In vitro studies have found that homotaurine is a GABAA partial agonist[9] as well as a GABAB receptor partial agonist with low efficacy, becoming an antagonist and displacing the full agonists GABA and baclofen at this receptor.[10] In a study in rats, homotaurine reversed the catatonia induced by baclofen (the prototypical GABAB agonist),[11] and was able to produce analgesia via the GABAB receptor, an effect that was abolished when CGP-35348, a GABAB receptor antagonist was applied.[12][13]

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.[14] Acamprosate was approved by the FDA in 2004 to treat alcohol dependence.[3]

References

  1. ^ "Homotaurine". Sigma-Aldrich.
  2. ^ Martorana, A.; Di Lorenzo, F.; Manenti, G.; Semprini, R.; Koch, G. (2014). "Homotaurine Induces Measurable Changes of Short Latency Afferent Inhibition in a Group of Mild Cognitive Impairment Individuals". Frontiers in Aging Neuroscience. 6: 254. doi:10.3389/fnagi.2014.00254. PMC 4172065. PMID 25295005.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ 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)
  4. ^ a b Caltagirone, C.; Ferrannini, L.; Marchionni, N.; Nappi, G.; Scapagnini, G.; Trabucchi, M. (2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: A review". Aging Clinical and Experimental Research. 24 (6): 580–7. doi:10.3275/8585. PMID 22961121. S2CID 10816430.
  5. ^ http://www.jgerontology-geriatrics.com/wp-content/uploads/2018/03/03_Martorana-1.pdf
  6. ^ Aisen, Paul; Gauthier, Serge; Vellas, Bruno; Briand, Richard; Saumier, Daniel; Laurin, Julie; Garceau, Denis (2007). "Alzhemed: A Potential Treatment for Alzheimers Disease". Current Alzheimer Research. 4 (4): 473–478. doi:10.2174/156720507781788882. PMID 17908052.
  7. ^ a b Oja SS and Kontro P. (2013). Lajtha ANS (ed.). Chapter 18: Taurine. Springer Science & Business Media. p. 520. ISBN 9781468443677. {{cite book}}: |work= ignored (help)
  8. ^ 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
  9. ^ Reyes-Haro, Daniel; Cabrera-Ruíz, Elizabeth; Estrada-Mondragón, Argel; Miledi, Ricardo; Martínez-Torres, Ataúlfo (2014). "Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs". Amino Acids. 46 (11): 2587–2593. doi:10.1007/s00726-014-1813-0. PMID 25119985. S2CID 10319072.
  10. ^ Giotti, A.; Luzzi, S.; Spagnesi, S.; Zilletti, Lucilla (1983). "Homotaurine: A GABAB antagonist in guinea-pig ileum". British Journal of Pharmacology. 79 (4): 855–862. doi:10.1111/j.1476-5381.1983.tb10529.x. PMC 2044932. PMID 6652358.
  11. ^ Mehta, A.; Ticku, M. (1987). "Baclofen induces catatonia in rats". Neuropharmacology. 26 (9): 1419–1423. doi:10.1016/0028-3908(87)90108-0. PMID 2823166. S2CID 24010833.
  12. ^ Serrano, M.Isabel; Serrano, Jose S.; Fernández, Ana; Asadi, Ihklas; Serrano-Martino, M.Carmen (1998). "GABAB Receptors and Opioid Mechanisms Involved in Homotaurine-Induced Analgesia". General Pharmacology: The Vascular System. 30 (3): 411–415. doi:10.1016/s0306-3623(97)00279-6. PMID 9510095.
  13. ^ Serrano, Maria Isabel; Serrano, Jose S.; Asadi, Ikhlas; Fernandez, Ana; Serrano-Martino, Maria Carmen (2001). "Role of K+-channels in homotaurine-induced analgesia". Fundamental and Clinical Pharmacology. 15 (3): 167–173. doi:10.1046/j.1472-8206.2001.00026.x. PMID 11468027.
  14. ^ Olive, M.Foster; Nannini, Michelle A.; Ou, Christine J.; Koenig, Heather N.; Hodge, Clyde W. (2002). "Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release". European Journal of Pharmacology. 437 (1–2): 55–61. doi:10.1016/s0014-2999(02)01272-4. PMID 11864639.
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