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 |
EC Number |
|
KEGG | |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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]
Acamprosate (N-acetyl homotaurine) was approved by the FDA in 2004 to treat alcohol dependence. [4]
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]
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 |
EC Number |
|
KEGG | |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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]
Acamprosate (N-acetyl homotaurine) was approved by the FDA in 2004 to treat alcohol dependence. [4]
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]