Gaboxadol

Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the alkaloid muscimol that was first synthesized in 1977 by the Danish 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 in a different way from benzodiazepines, Z-Drugs, and barbiturates. Lundbeck states that gaboxadol also increases deep sleep (stage 4). Unlike benzodiazepines, THIP does not demonstrate reinforcement in mice or baboons despite activation of dopaminergic neurons in the ventral tegmental area.[3]

Gaboxadol
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.059.039
Chemical and physical data
FormulaC6H8N2O2
Molar mass140.142 g·mol−1
3D model (JSmol)
SMILES
  • O=C1/C2=C(\ON1)CNCC2
InChI
  • InChI=1S/C6H8N2O2/c9-6-4-1-2-7-3-5(4)10-8-6/h7H,1-3H2,(H,8,9) Y
  • Key:ZXRVKCBLGJOCEE-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

In 2015, Lundbeck sold its rights to the molecule to Ovid Therapeutics, whose plan is to develop it for FXS and Angelman syndrome.[4] It is known internally in Ovid as OV101.

See also

References
  1. Morris H (August 2013). "Gaboxadol". Harper's Magazine. August 2013. Retrieved 2014-11-20.
  2. US Patent 4278676 - Heterocyclic compounds
  3. Vashchinkina E, Panhelainen A, Vekovischeva OY, Aitta-aho T, Ebert B, Ator NA, Korpi ER (April 2012). "GABA site agonist gaboxadol induces addiction-predicting persistent changes in ventral tegmental area dopamine neurons but is not rewarding in mice or baboons". The Journal of Neuroscience. 32 (15): 5310–20. doi:10.1523/JNEUROSCI.4697-11.2012. PMC 6622081. PMID 22496576.
  4. Tirrell M (16 April 2015). "Former Teva CEO's new gig at Ovid Therapeutics". CNBC. Retrieved 2015-05-06.
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