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| OtherNames = Tramiprosate; Alzhemed; 3-APS
| OtherNames = Tramiprosate; Alzhemed; 3-APS
|Section1={{Chembox Identifiers
|Section1={{Chembox Identifiers
⚫
| CASNo_Ref = {{cascite|correct|??}}
⚫
| CASNo = 3687-18-1
| ChEBI = 1457
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1584
| ChemSpiderID = 1584
⚫
| ChEMBL_Ref = {{ebicite|correct|EBI}}
⚫
| ChEMBL = 149082
| DrugBank = DB06527
| EC_number = 222-977-4
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D06202
| KEGG = D06202
⚫
| PubChem = 1646
⚫
| UNII_Ref = {{fdacite|correct|FDA}}
⚫
| UNII = 5K8EAX0G53
| InChI = 1/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7)
| InChI = 1/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7)
| InChIKey = SNKZJIOFVMKAOJ-UHFFFAOYAT
| InChIKey = SNKZJIOFVMKAOJ-UHFFFAOYAT
⚫
| ChEMBL_Ref = {{ebicite|correct|EBI}}
⚫
| ChEMBL = 149082
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7)
| StdInChI = 1S/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SNKZJIOFVMKAOJ-UHFFFAOYSA-N
| StdInChIKey = SNKZJIOFVMKAOJ-UHFFFAOYSA-N
⚫
| CASNo_Ref = {{cascite|correct|??}}
⚫
| CASNo = 3687-18-1
⚫
| UNII_Ref = {{fdacite|correct|FDA}}
⚫
| UNII = 5K8EAX0G53
⚫
| PubChem = 1646
| SMILES = O=S(=O)(O)CCCN
| SMILES = O=S(=O)(O)CCCN
}}
}}
Line 44: Line 47:
| FlashPt =
| FlashPt =
| AutoignitionPt =
| AutoignitionPt =
| GHS_ref=<ref>{{cite web |title=Tramiprosate |url=https://pubchem.ncbi.nlm.nih.gov/compound/1646#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |access-date=13 December 2021 |language=en}}</ref>
| RPhrases ={{R36/37/38}}
| SPhrases ={{S26}} {{S36}}
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|315|319|335}}
| PPhrases = {{P-phrases|261|264|271|280|302+352|304+340|305+351+338|312|321|332+313|337+313|362|403+233|405|501}}
}}
}}
}}
}}


'''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 sulfonic acid found in seaweed.<ref>{{cite journal |last1=Martorana |first1=Alessandro |last2=Di Lorenzo |first2=Francesco |last3=Manenti |first3=Guglielmo |last4=Semprini |first4=Roberta |last5=Koch |first5=Giacomo |title=Homotaurine Induces Measurable Changes of Short Latency Afferent Inhibition in a Group of Mild Cognitive Impairment Individuals |journal=Frontiers in Aging Neuroscience |date=23 September 2014 |volume=6 |page=254 |doi=10.3389/fnagi.2014.00254 |pmid=25295005 |pmc=4172065 |doi-access=free }}</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]] (AD) that did not show efficacy. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a [[Disease-modifying treatment|disease-modifying effect]].<ref name=AD2012rev>{{cite journal |last1=Caltagirone |first1=C |last2=Ferrannini |first2=L |last3=Marchionni |first3=N |last4=Nappi |first4=G |last5=Scapagnini |first5=G |last6=Trabucchi |first6=M |title=The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review |journal=Aging Clinical and Experimental Research |date=December 2012 |volume=24 |issue=6 |pages=580–587 |doi=10.3275/8585 |pmid=22961121 |s2cid=10816430 }}</ref> A study in cognitive impairment done in 2018 did show positive benefits.<ref>{{cite journal |last1=Martorana |first1=A. |last2=Motta |first2=C |last3=Koch |first3=G. |last4=Massaia |first4=M. |last5=Mondino |first5=S. |last6=Raniero |first6=I. |last7=Vacca |first7=A. |last8=Di Lorenzo |first8=F. |last9=Cavallo |first9=G. |last10=Oddenino |first10=E. |last11=Pavanelli |first11=E. |last12=Maniscalco |first12=M. |last13=Montano |first13=V. |last14=Mastropietro |first14=A. |last15=Bellia |first15=N. C. |last16=Ciravegna |first16=E. |last17=La Rocca |first17=M. |last18=Vitale |first18=E. |last19=Lorico |first19=F. |last20=Zacchettin |first20=B. |last21=Scalise |first21=A. |last22=Codemo |first22=A. |last23=Gabelli |first23=C. |last24=Spano |first24=M. |last25=Poli |first25=S. |last26=Panuccio |first26=D. |last27=Bruno |first27=P. |last28=Alfieri |first28=P. |last29=Ruggiero |first29=R. |last30=Cursi |first30=F. |last31=Levi Della Vida |first31=G. |title=Effect of homotaurine in patients with cognitive impairment: results from an Italian observational retrospective study |journal=Journal of Gerontology and Geriatrics |date=15 March 2018 |volume=66 |pages=15–20 |url=http://www.jgerontology-geriatrics.com/article/view/97 }}</ref>


Homotaurine is currently in a phase 3 study with expected FDA approval as the first disease modifying drug for AD.<ref name="Tolar et al 2020">{{cite journal |last1=Tolar |first1=Martin |last2=Abushakra |first2=Susan |last3=Hey |first3=John A. |last4=Porsteinsson |first4=Anton |last5=Sabbagh |first5=Marwan |title=Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval |journal=Alzheimer's Research & Therapy |date=December 2020 |volume=12 |issue=1 |pages=95 |doi=10.1186/s13195-020-00663-w |pmid=32787971 |pmc=7424995 |doi-access=free }}</ref><ref>{{cite journal |last1=Abushakra |first1=S. |last2=Porsteinsson |first2=A. |last3=Scheltens |first3=P. |last4=Sadowsky |first4=C. |last5=Vellas |first5=B. |last6=Cummings |first6=J. |last7=Gauthier |first7=S. |last8=Hey |first8=J. A. |last9=Power |first9=A. |last10=Wang |first10=P. |last11=Tolar |first11=M. |last12=Tolar |first12=M |title=Clinical effects of tramiprosate in apoe4/4 homozygous patients with mild alzheimer's disease suggest disease modification potential |journal=Journal of Prevention of Alzheimer's Disease |date=1 September 2017 |volume=4 |issue=3 |pages=149–156 |doi=10.14283/jpad.2017.26 |pmid=29182706 |s2cid=44515548 |doi-access=free }}</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. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effects.<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>


==Medical use==
Homotaurine is currently in a phase 3 study with expected FDA approval as the first disease modifying drug for AD. <ref>https://pubmed.ncbi.nlm.nih.gov/32787971/</ref> <ref>https://pubmed.ncbi.nlm.nih.gov/29182706/</ref>
[[Acamprosate]] (''N''-acetyl homotaurine) was approved by the FDA in 2004 to treat [[alcohol dependence]].<ref name=OrgChem2007>{{cite book | last1 = Lednicer | first1 = Daniel | name-list-style = 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>


==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 |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 |title=Alzhemed: A Potential Treatment for Alzheimers Disease |journal=Current Alzheimer Research |date=1 September 2007 |volume=4 |issue=4 |pages=473–478 |doi=10.2174/156720507781788882 |pmid=17908052 }}</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 | 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| s2cid = 19694376}}</ref>
Homotaurine has been reported as a [[GABA]] antagonist,<ref name=OrgChem2007/> as well as a GABA agonist.<ref name=Metabolism2013>{{cite book |last1=Lajtha |first1=Abel |title=Metabolism in the Nervous System |date=2013 |publisher=Springer Science & Business Media |isbn=978-1-4684-4367-7 |page=520 |url=https://books.google.com/books?id=du_TBwAAQBAJ&pg=PA520 }}</ref><ref name=PharmPrinc2011>{{cite book |last1=Tashjian |first1=Armen H. |last2=Armstrong |first2=Ehrin J. |title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy |date=2011 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-1805-6 |page=308 |url=https://books.google.com/books?id=kjCCMZHInigC&pg=PA308 }}</ref> ''[[In vitro]]'' studies have found that homotaurine is a [[GABAA receptor|GABA<sub>A</sub>]] partial agonist<ref>{{cite journal |last1=Reyes-Haro |first1=Daniel |last2=Cabrera-Ruíz |first2=Elizabeth |last3=Estrada-Mondragón |first3=Argel |last4=Miledi |first4=Ricardo |last5=Martínez-Torres |first5=Ataúlfo |title=Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs |journal=Amino Acids |date=November 2014 |volume=46 |issue=11 |pages=2587–2593 |doi=10.1007/s00726-014-1813-0 |pmid=25119985 |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 |last1=Giotti |first1=A. |last2=Luzzi |first2=S. |last3=Spagnesi |first3=S. |last4=Zilletti |first4=L. |title=Homotaurine: a GABAB antagonist in guinea-pig ileum. |journal=British Journal of Pharmacology |date=August 1983 |volume=79 |issue=4 |pages=855–862 |doi=10.1111/j.1476-5381.1983.tb10529.x |pmid=6652358 |pmc=2044932 }}</ref> In a study in rats, homotaurine reversed the [[catatonia]] induced by [[baclofen]] (the prototypical GABA<sub>B</sub> agonist),<ref>{{cite journal |last1=Mehta |first1=A |last2=Ticku |first2=M |title=Baclofen induces catatonia in rats |journal=Neuropharmacology |date=September 1987 |volume=26 |issue=9 |pages=1419–1423 |doi=10.1016/0028-3908(87)90108-0 |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 |last1=Serrano |first1=M.Isabel |last2=Serrano |first2=Jose S. |last3=Fernández |first3=Ana |last4=Asadi |first4=Ihklas |last5=Serrano-Martino |first5=M.Carmen |title=GABAB Receptors and Opioid Mechanisms Involved in Homotaurine-Induced Analgesia |journal=General Pharmacology: The Vascular System |date=March 1998 |volume=30 |issue=3 |pages=411–415 |doi=10.1016/s0306-3623(97)00279-6 |pmid=9510095 }}</ref><ref>{{cite journal |last1=Serrano |first1=Maria Isabel |last2=Serrano |first2=Jose S. |last3=Asadi |first3=Ikhlas |last4=Fernandez |first4=Ana |last5=Serrano-Martino |first5=Maria Carmen |title=Role of K+-channels in homotaurine-induced analgesia |journal=Fundamental and Clinical Pharmacology |date=16 June 2001 |volume=15 |issue=3 |pages=167–173 |doi=10.1046/j.1472-8206.2001.00026.x |pmid=11468027 |s2cid=19694376 }}</ref>


In a human study homotaurine selectively and fully inhibits the formation of Aβ42 oligomers at the clinical dose, without evidence of vasogenic edema.<ref>https://pubmed.ncbi.nlm.nih.gov/32787971/</ref>
In a human study homotaurine selectively and fully inhibits the formation of Aβ42 oligomers at the clinical dose, without evidence of vasogenic edema.<ref name="Tolar et al 2020"/>


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-style = 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 |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 |title=Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release |journal=European Journal of Pharmacology |date=February 2002 |volume=437 |issue=1–2 |pages=55–61 |doi=10.1016/s0014-2999(02)01272-4 |pmid=11864639 }}</ref>


== References ==
== References ==

Latest revision as of 19:21, 6 August 2024

Homotaurine[1]
Skeletal formula
Ball-and-stick model
Names
Preferred IUPAC name
3-Aminopropane-1-sulfonic acid
Other names
Tramiprosate; Alzhemed; 3-APS
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.020.889 Edit this at Wikidata
EC Number
  • 222-977-4
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)
Hazards
GHS labelling:[2]
GHS07: Exclamation mark
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
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 sulfonic acid found in seaweed.[3] It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.[4]

Homotaurine was investigated in a Phase III clinical trial as a potential treatment for Alzheimer's disease (AD) that did not show efficacy. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effect.[5] A study in cognitive impairment done in 2018 did show positive benefits.[6]

Homotaurine is currently in a phase 3 study with expected FDA approval as the first disease modifying drug for AD.[7][8]

Medical use

[edit]

Acamprosate (N-acetyl homotaurine) was approved by the FDA in 2004 to treat alcohol dependence.[4]

Biochemical properties

[edit]

In preclinical studies it had been found to bind to soluble amyloid beta and inhibit the formation of neurotoxic aggregates.[5][9] Homotaurine has also shown anticonvulsant activities, reduction in skeletal muscle tonus, and hypothermic activity.[10]

Homotaurine has been reported as a GABA antagonist,[4] as well as a GABA agonist.[10][11] In vitro studies have found that homotaurine is a GABAA partial agonist[12] 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.[13] In a study in rats, homotaurine reversed the catatonia induced by baclofen (the prototypical GABAB agonist),[14] and was able to produce analgesia via the GABAB receptor, an effect that was abolished when CGP-35348, a GABAB receptor antagonist was applied.[15][16]

In a human study homotaurine selectively and fully inhibits the formation of Aβ42 oligomers at the clinical dose, without evidence of vasogenic edema.[7]

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.[17]

References

[edit]
  1. ^ "Homotaurine". Sigma-Aldrich.
  2. ^ "Tramiprosate". pubchem.ncbi.nlm.nih.gov. Retrieved 13 December 2021.
  3. ^ Martorana, Alessandro; Di Lorenzo, Francesco; Manenti, Guglielmo; Semprini, Roberta; Koch, Giacomo (23 September 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.
  4. ^ a b c Lednicer D (2008). The Organic Chemistry of Drug Synthesis (7th ed.). Hoboken: John Wiley & Sons. p. 15. ISBN 978-0-470-18066-2.
  5. ^ a b Caltagirone, C; Ferrannini, L; Marchionni, N; Nappi, G; Scapagnini, G; Trabucchi, M (December 2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review". Aging Clinical and Experimental Research. 24 (6): 580–587. doi:10.3275/8585. PMID 22961121. S2CID 10816430.
  6. ^ Martorana, A.; Motta, C; Koch, G.; Massaia, M.; Mondino, S.; Raniero, I.; Vacca, A.; Di Lorenzo, F.; Cavallo, G.; Oddenino, E.; Pavanelli, E.; Maniscalco, M.; Montano, V.; Mastropietro, A.; Bellia, N. C.; Ciravegna, E.; La Rocca, M.; Vitale, E.; Lorico, F.; Zacchettin, B.; Scalise, A.; Codemo, A.; Gabelli, C.; Spano, M.; Poli, S.; Panuccio, D.; Bruno, P.; Alfieri, P.; Ruggiero, R.; Cursi, F.; Levi Della Vida, G. (15 March 2018). "Effect of homotaurine in patients with cognitive impairment: results from an Italian observational retrospective study". Journal of Gerontology and Geriatrics. 66: 15–20.
  7. ^ a b Tolar, Martin; Abushakra, Susan; Hey, John A.; Porsteinsson, Anton; Sabbagh, Marwan (December 2020). "Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval". Alzheimer's Research & Therapy. 12 (1): 95. doi:10.1186/s13195-020-00663-w. PMC 7424995. PMID 32787971.
  8. ^ Abushakra, S.; Porsteinsson, A.; Scheltens, P.; Sadowsky, C.; Vellas, B.; Cummings, J.; Gauthier, S.; Hey, J. A.; Power, A.; Wang, P.; Tolar, M.; Tolar, M (1 September 2017). "Clinical effects of tramiprosate in apoe4/4 homozygous patients with mild alzheimer's disease suggest disease modification potential". Journal of Prevention of Alzheimer's Disease. 4 (3): 149–156. doi:10.14283/jpad.2017.26. PMID 29182706. S2CID 44515548.
  9. ^ Aisen, Paul; Gauthier, Serge; Vellas, Bruno; Briand, Richard; Saumier, Daniel; Laurin, Julie; Garceau, Denis (1 September 2007). "Alzhemed: A Potential Treatment for Alzheimers Disease". Current Alzheimer Research. 4 (4): 473–478. doi:10.2174/156720507781788882. PMID 17908052.
  10. ^ a b Lajtha, Abel (2013). Metabolism in the Nervous System. Springer Science & Business Media. p. 520. ISBN 978-1-4684-4367-7.
  11. ^ Tashjian, Armen H.; Armstrong, Ehrin J. (2011). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins. p. 308. ISBN 978-1-4511-1805-6.
  12. ^ Reyes-Haro, Daniel; Cabrera-Ruíz, Elizabeth; Estrada-Mondragón, Argel; Miledi, Ricardo; Martínez-Torres, Ataúlfo (November 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.
  13. ^ Giotti, A.; Luzzi, S.; Spagnesi, S.; Zilletti, L. (August 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.
  14. ^ Mehta, A; Ticku, M (September 1987). "Baclofen induces catatonia in rats". Neuropharmacology. 26 (9): 1419–1423. doi:10.1016/0028-3908(87)90108-0. PMID 2823166. S2CID 24010833.
  15. ^ Serrano, M.Isabel; Serrano, Jose S.; Fernández, Ana; Asadi, Ihklas; Serrano-Martino, M.Carmen (March 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.
  16. ^ Serrano, Maria Isabel; Serrano, Jose S.; Asadi, Ikhlas; Fernandez, Ana; Serrano-Martino, Maria Carmen (16 June 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. S2CID 19694376.
  17. ^ Olive, M.Foster; Nannini, Michelle A; Ou, Christine J; Koenig, Heather N; Hodge, Clyde W (February 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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