Homotaurine

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Homotaurine[1]
Skeletal formula
Ball-and-stick model
Names
IUPAC name
3-Aminopropane-1-sulfonic acid
Other names
Tramiprosate; Alzhemed; 3-APS
Identifiers
3D model (Jmol)
ChemSpider
ECHA InfoCard 100.020.889
KEGG
Properties
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.[5][6] In vitro studies have found that homotaurine is a GABAA partial agonist[7] as well as a GABAB 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 GABAB agonist),[9] and was able to produce analgesia via the GABAB receptor, an effect that was abolished when CGP 35348, a GABAB 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]

See also[edit]

References[edit]

  1. ^ Homotaurine at Sigma-Aldrich
  2. ^ 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. 
  3. ^ a b Caltagirone C; et al. (Dec 2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review". Aging Clin Exp Res. 24 (6): 580–7. doi:10.3275/8585. 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. ^ a b 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. (2014). "Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.". Amino Acids. 46: 2587–93. doi:10.1007/s00726-014-1813-0. PMID 25119985. 
  8. ^ Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983). "Homotaurine: a GABAB antagonist in guinea-pig ileum.". Br. J. Pharmacol. 79: 855–62. doi:10.1111/j.1476-5381.1983.tb10529.x. PMC 2044932Freely accessible. PMID 6652358. 
  9. ^ Mehta AK1, Ticku MK. (1987). "Baclofen induces catatonia in rats.". Neuropharmacology. 26: 1419–23. doi:10.1016/0028-3908(87)90108-0. PMID 2823166. 
  10. ^ Serrano MI1, Serrano JS, Fernández A, Asadi I, Serrano-Martino MC. (1998). "GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.". Gen. Pharmacol. 30: 411–5. doi:10.1016/s0306-3623(97)00279-6. PMID 9510095. 
  11. ^ Serrano MI1, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. (2001). "Role of K+ -channels in homotaurine-induced analgesia.". Fundam Clin Pharmacol. 15: 167–73. doi:10.1046/j.1472-8206.2001.00026.x. PMID 11468027. 
  12. ^ Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW (2002). "Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.". Eur. J. Pharmacol. 437: 55–61. doi:10.1016/s0014-2999(02)01272-4. PMID 11864639.