Homotaurine
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Names | |
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| 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] | |
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| 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).
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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
Acamprosate (N-acetyl homotaurine) was approved by the FDA in 2004 to treat alcohol dependence.[4]
Biochemical properties
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]