THAZ

THAZ
Clinical data
Drug classGABAA-ρ receptor antagonist; GABAA receptor antagonist; Glycine receptor antagonist
ATC code
  • None
Identifiers
  • 5,6,7,8-tetrahydro-4H-[1,2]oxazolo[4,5-d]azepin-3-one
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC7H10N2O2
Molar mass154.169 g·mol−1
3D model (JSmol)
  • C1CNCCC2=C1C(=O)NO2
  • InChI=1S/C7H10N2O2/c10-7-5-1-3-8-4-2-6(5)11-9-7/h8H,1-4H2,(H,9,10)
  • Key:KHTRGFVHYPWHIZ-UHFFFAOYSA-N

THAZ, also known as 5,6,7,8-tetrahydro-4H-isoxazolo(4,5-d)azepin-3-ol, is a moderately potent GABAA-ρ receptor antagonist related to gaboxadol (THIP). Unlike gaboxadol, it is said to be virtually inactive at the GABAA receptor. However, in other studies, it showed significant affinity for the GABAA receptor, where it appeared to act as an antagonist. In addition to its GABAA-ρ receptor antagonism, THAZ is a very weak glycine receptor antagonist. In contrast to muscimol and gaboxadol, THAZ injected directly into the brain produced convulsions. The drug was first described in the scientific literature by Povl Krogsgaard-Larsen and colleagues by 1979. Derivatives of THAZ such as N-Bn-THAZ and O-Bn-THAZ have been found to act as serotonin 5-HT2A and 5-HT2C receptor agonists.

See also

References

  1. 1 2 Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P (August 2002). "GABA(A) receptor ligands and their therapeutic potentials". Current Topics in Medicinal Chemistry. 2 (8): 817–832. doi:10.2174/1568026023393525. PMID 12171573. Like thio-THIP, the structurally related THIP analogues, aza-THIP, iso-THIP and THAZ (Fig. 4) are virtually inactive at the GABAA receptors [51, 52], but disclose antagonistic effects at the GABAC receptors [53].
  2. 1 2 3 Krehan D, Frølund B, Ebert B, Nielsen B, Krogsgaard-Larsen P, Johnston GA, et al. (November 2003). "Aza-THIP and related analogues of THIP as GABA C antagonists". Bioorganic & Medicinal Chemistry. 11 (23): 4891–4896. doi:10.1016/j.bmc.2003.09.016. PMID 14604650.
  3. 1 2 3 Arnt J, Krogsgaard-Larsen P (November 1979). "GABA agonists and potential antagonists related to muscimol". Brain Research. 177 (2): 395–400. doi:10.1016/0006-8993(79)90793-5. PMID 227538.
  4. ↑ Krogsgaard-Larsen P, Hjeds H, Curtis DR, Leah JD, Peet MJ (November 1982). "Glycine antagonists structurally related to muscimol, THIP, or isoguvacine". Journal of Neurochemistry. 39 (5): 1319–1324. doi:10.1111/j.1471-4159.1982.tb12573.x. PMID 6288870.
  5. ↑ Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
  6. ↑ Jensen AA, Plath N, Pedersen MH, Isberg V, Krall J, Wellendorph P, et al. (February 2013). "Design, synthesis, and pharmacological characterization of N- and O-substituted 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol analogues: novel 5-HT(2A)/5-HT(2C) receptor agonists with pro-cognitive properties". Journal of Medicinal Chemistry. 56 (3): 1211–1227. doi:10.1021/jm301656h. PMID 23301527.