Homotaurine: Difference between revisions
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'''Homotaurine''' (also known as '''tramiprosate''' ([[International Nonproprietary Name|INN]]), '''3-amino-1-propanesulfonic acid''', or '''3-APS''') is a natural |
'''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/> |
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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 |
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> |
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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 }}</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 }}</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> |
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| ⚫ | [[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> |
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==Biochemical properties== |
==Biochemical properties== |
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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> |
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> |
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| ⚫ | |||
| ⚫ | 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> |
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== References == |
== References == |
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Latest revision as of 19:21, 6 August 2024
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| Names | |
|---|---|
| Preferred IUPAC name
3-Aminopropane-1-sulfonic acid | |
| Other names
Tramiprosate; Alzhemed; 3-APS
| |
| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
| ECHA InfoCard | 100.020.889 |
| EC Number |
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| KEGG | |
PubChem CID
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|
| UNII | |
CompTox Dashboard (EPA)
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| |
| |
| Properties | |
| C3H9NO3S | |
| Molar mass | 139.17 g·mol−1 |
| Melting point | 293 °C (559 °F; 566 K) (decomposition) |
| Hazards | |
| GHS labelling:[2] | |
| |
| 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).
| |
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]- ^ "Homotaurine". Sigma-Aldrich.
- ^ "Tramiprosate". pubchem.ncbi.nlm.nih.gov. Retrieved 13 December 2021.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b Lajtha, Abel (2013). Metabolism in the Nervous System. Springer Science & Business Media. p. 520. ISBN 978-1-4684-4367-7.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.