Homotaurine

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^[1]

Names
Preferred IUPAC name 3-Aminopropane-1-sulfonic acid
Other names Tramiprosate; Alzhemed; 3-APS
Identifiers
CAS Number	3687-18-1 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:1457
ChEMBL	ChEMBL149082 Y
ChemSpider	1584 Y
DrugBank	DB06527
ECHA InfoCard	100.020.889
EC Number	222-977-4
KEGG	D06202 Y
PubChem CID	1646
UNII	5K8EAX0G53 Y
CompTox Dashboard (EPA)	DTXSID80190352
InChI InChI=1S/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7) Y Key: SNKZJIOFVMKAOJ-UHFFFAOYSA-N Y InChI=1/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7) Key: SNKZJIOFVMKAOJ-UHFFFAOYAT
SMILES O=S(=O)(O)CCCN
Properties
Chemical formula	C3H9NO3S
Molar mass	139.17 g·mol−1
Melting point	293 °C (559 °F; 566 K) (decomposition)
Hazards
GHS labelling:[2]
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Precautionary statements	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). Y verify (what is YN ?) Infobox references

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 GABA_A partial agonist^[12] as well as a GABA_B 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 GABA_B agonist),^[14] and was able to produce analgesia via the GABA_B receptor, an effect that was abolished when CGP-35348, a GABA_B 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]