Gaboxadol

Gaboxadol

Gaboxadol
Systematic (IUPAC) name
4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one
Identifiers
CAS Registry Number  N
ATC code None
PubChem CID:
IUPHAR/BPS
ChemSpider  Y
UNII  Y
KEGG  Y
ChEMBL  Y
Chemical data
Formula C6H8N2O2
Molecular mass 140.14 g/mol
 N   

Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the Amanita muscaria alkaloid muscimol that was first synthesized in 1977 by the Danish medicinal chemist Povl Krogsgaard-Larsen.[1] In the early 1980s gaboxadol was the subject of a series of pilot studies that tested its efficacy as an analgesic and anxiolytic, as well as a treatment for tardive dyskinesia, Huntington's disease, Alzheimer's disease, and spasticity.[1] It was not until 1996 that researchers attempted to harness gaboxadol's frequently reported sedative "adverse effect" for the treatment of insomnia, resulting in a series of clinical trials sponsored by Lundbeck and Merck.[1][2] In March, 2007, Merck and Lundbeck cancelled work on the drug, citing safety concerns and the failure of an efficacy trial. It acts on the GABA system, but possibly in a different way from benzodiazepines, nonbenzodiazepines and barbiturates - (Sodium Pentothal, etc.). Lundbeck states that gaboxadol also increases deep sleep (stage 4). It is, however, not reinforcing like benzodiazepines are.[3]

In 2015, Lundbeck sold its gaboxadol rights to medical startup Ovid Therapeutics, whose plan is to develop it for treating fragile X syndrome and Angelman Syndrome.[4]

See also

References

  1. ^ a b c Morris, Hamilton (August 2013). "Gaboxadol". Harper's Magazine. Retrieved 2014-11-20. 
  2. ^ US Patent 4278676 - Heterocyclic compounds
  3. ^ Vashchinkina, E; Panhelainen, A; Vekovischeva, O. Y.; Aitta-Aho, T; Ebert, B; Ator, N. A.; Korpi, E. R. (2012). "GABA site agonist gaboxadol induces addiction-predicting persistent changes in ventral tegmental area dopamine neurons but is not rewarding in mice or baboons". Journal of Neuroscience 32 (15): 5310–20.  
  4. ^ Tirrell, Meg (16 April 2015). "Former Teva CEO's new gig at Ovid Therapeutics". CNBC. Retrieved 2015-05-06. 

External links

  • 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol at the US National Library of Medicine Medical Subject Headings (MeSH)
  • H. Lundbeck Website
  • Medical News Today article
  • Report of cancellation of development.
  • Gaboxadol