Thio-4-PIOL

Last updated

Thio-4-PIOL
Thio-4-PIOL.svg
Clinical data
Other names5-(Piperidin-4-yl)isothiazol-3-ol
Drug class GABAA receptor weak partial agonist or antagonist
ATC code
  • None
Identifiers
  • 5-piperidin-4-yl-1,2-thiazol-3-one
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
Formula C8H12N2OS
Molar mass 184.26 g·mol−1
3D model (JSmol)
  • C1CNCCC1C2=CC(=O)NS2
  • InChI=1S/C8H12N2OS/c11-8-5-7(12-10-8)6-1-3-9-4-2-6/h5-6,9H,1-4H2,(H,10,11)
  • Key:WUINUICOEAZPLK-UHFFFAOYSA-N

Thio-4-PIOL, also known as 5-(piperidin-4-yl)isothiazol-3-ol, is a GABAA receptor weak partial agonist or antagonist related to 4-PIOL. [1] [2] [3] [4]

Contents

Pharmacology

The drug acts as a weak partial agonist or antagonist of the GABAA receptor, with varying efficacy depending on the receptor complex's specific subunit composition. [1] [4] It shows Emax Tooltip maximal efficacy values of up to approximately 30% at α5β3γ2S, α4β3δ, and α6β3δ GABAA receptors, 4 to 12% at α5β2γ2S, α4β2δ, and α6β2δ GABAA receptors, and 0 to 4% at α1β3γ2S, α1β2γ2S, α2β2γ2S, α2β3γ2S, α3β2γ2S, and α3β3γ2S GABAA receptors. [1] [4] Thio-4-PIOL shows greater efficacy at extrasynaptic GABAA receptors than at synaptic receptors. [5] [1] [4] It produces effects in animals including hypolocomotion and hyperlocomotion (dependent on dose), anxiogenic effects, pronociceptive effects, impaired spatial learning, and seizures. [4]

Development

Thio-4-PIOL was first described in the scientific literature by 1997. [6] [7] The drug is unlikely to be a candidate for a therapeutic drug due to its undesirable effects, but may be useful in scientific research. [4] It is one of the only GABAA receptor agonists to have been comprehensively evaluated in terms of functional activities. [4]

See also

References

  1. 1 2 3 4 Krall J, Balle T, Krogsgaard-Larsen N, Sørensen TE, Krogsgaard-Larsen P, Kristiansen U, et al. (2015). "GABAA receptor partial agonists and antagonists: structure, binding mode, and pharmacology". Diversity and Functions of GABA Receptors: A Tribute to Hanns Möhler, Part A. Advances in Pharmacology. Vol. 72. pp. 201–227. doi:10.1016/bs.apha.2014.10.003. ISBN   978-0-12-802660-1. PMID   25600372.
  2. ↑ Krogsgaard-Larsen P, Frølund B, Liljefors T (2002). "Specific GABA(A) agonists and partial agonists". Chemical Record. 2 (6): 419–430. doi:10.1002/tcr.10040. PMID   12469353.
  3. ↑ 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.
  4. 1 2 3 4 5 6 7 Hoestgaard-Jensen K, O'Connor RM, Dalby NO, Simonsen C, Finger BC, Golubeva A, et al. (October 2013). "The orthosteric GABAA receptor ligand Thio-4-PIOL displays distinctly different functional properties at synaptic and extrasynaptic receptors". British Journal of Pharmacology. 170 (4): 919–932. doi:10.1111/bph.12340. PMC   3799604 . PMID   23957253.
  5. ↑ Johnston GA (October 2014). "Muscimol as an ionotropic GABA receptor agonist". Neurochemical Research. 39 (10): 1942–1947. doi:10.1007/s11064-014-1245-y. PMID   24473816. As with THIP, 4-PIOL and its analogues show differences in activity at synaptic and extrasynaptic GABAA receptors with thio-4-PIOL showing partial agonist responses up to 30 % of GABA on extrasynaptic receptors with little partial agonist response (0-4 % of GABA) at synaptic receptors [48].
  6. ↑ Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA (December 1997). "Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors". Molecular Pharmacology. 52 (6): 1150–1156. doi:10.1124/mol.52.6.1150. PMID   9396785.
  7. ↑ Westh-Hansen SE, Rasmussen PB, Hastrup S, Nabekura J, Noguchi K, Akaike N, et al. (June 1997). "Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit". European Journal of Pharmacology. 329 (2–3): 253–257. doi:10.1016/S0014-2999(97)89186-8. PMID   9226420.
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