Homotaurine

Homotaurine^[1]

Names
IUPAC name 3-Aminopropane-1-sulfonic acid
Other names Tramiprosate; Alzhemed; 3-APS
Identifiers
CAS Number	3687-18-1
ChEMBL	ChEMBL149082
ChemSpider	1584
Jmol interactive 3D	Image
KEGG	D06202
PubChem	1646
InChI InChI=1S/C3H9NO3S/c4-2-1-3-8(5,6)7/h1-4H2,(H,5,6,7) Key: SNKZJIOFVMKAOJ-UHFFFAOYSA-N 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
R-phrases	R36/37/38
S-phrases	S26 S36
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Homotaurine (3-amino-1-propanesulfonic acid (3-APS) or tramiprosate (INN)) is a synthetic organic compound. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which is it resembles.^[2]

Homotaurine was investigated in a Phase III clinical trial as a potential treatment for Alzheimer's disease that did not show efficacy in its primary endpoints.^[3] In preclinical studies it had been found to bind to soluble amyloid beta and inhibit the formation of neurotoxic aggregates.^[3][4] Homotaurine has also shown anticonvulsant activities, reduction in skeletal muscle tonus, and hypothermic activity.^[5]

Homotaurine has been reported as a GABA antagonist^[2] as well as a GABA agonist.^[6][5] In vitro studies have found that homotaurine is a GABA_A partial agonist^[7] as well as a GABA_B receptor partial agonist with low efficacy, becoming an antagonist and a displacing full agonist of GABA or baclofen at this receptor.^[8] In a study in rats, homotaurine reversed the catatonia induced by baclofen (the prototypical GABA_B agonist),^[9] 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.^[10][11]

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 acamprosate.^[12] Acamprosate, the N-acetyl derivative of homotaurine, was approved by the FDA in 2004 to treat alcohol dependence.^[2]

References

1. Homotaurine at Sigma-Aldrich
2. Lednicer D (2008). The Organic Chemistry of Drug Synthesis (7th ed.). Hoboken: John Wiley & Sons. p. 15. ISBN 978-0-470-18066-2.
3. Caltagirone C et al. The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review. Aging Clin Exp Res. 2012 Dec;24(6):580-7. PMID 22961121
4. Aisen PS, Gauthier S, Vellas B, Briand R, Saumier D, Laurin J, Garceau D (2007). "Alzhemed: a potential treatment for Alzheimer's disease". Current Alzheimer Research 4 (4): 473–8. doi:10.2174/156720507781788882. PMID 17908052.
5. Oja SS and Kontro P. Taurine. Chapter 18 in Metabolism in the Nervous System, Ed. Lajtha ANS. Springer Science & Business Media, 2013. ISBN 9781468443677. Page 520
6. 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. Page 308
7. Reyes-Haro D1, Cabrera-Ruíz E, Estrada-Mondragón A, Miledi R, Martínez-Torres A. "Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.". PMID 25119985.
8. Giotti A, Luzzi S, Spagnesi S, Zilletti L. "Homotaurine: a GABAB antagonist in guinea-pig ileum.". PMID 6652358.
9. Mehta AK1, Ticku MK. "Baclofen induces catatonia in rats.". PMID 2823166.
10. Serrano MI1, Serrano JS, Fernández A, Asadi I, Serrano-Martino MC. "GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.". PMID 9510095.
11. Serrano MI1, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. "Role of K+ -channels in homotaurine-induced analgesia.". PMID 11468027.
12. Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW. "Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.". PMID 11864639.