Chemistry:Thio-4-PIOL

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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]

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 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. ↑ 1.0 1.1 1.2 1.3 "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. 72. 2015. pp. 201–227. doi:10.1016/bs.apha.2014.10.003. ISBN 978-0-12-802660-1. 
  2. ↑ "Specific GABA(A) agonists and partial agonists". Chemical Record 2 (6): 419–430. 2002. doi:10.1002/tcr.10040. PMID 12469353. 
  3. ↑ "GABA(A) receptor ligands and their therapeutic potentials". Current Topics in Medicinal Chemistry 2 (8): 817–832. August 2002. doi:10.2174/1568026023393525. PMID 12171573. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "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. October 2013. doi:10.1111/bph.12340. PMID 23957253. 
  5. ↑ "Muscimol as an ionotropic GABA receptor agonist". Neurochemical Research 39 (10): 1942–1947. October 2014. 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. ↑ "Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors". Molecular Pharmacology 52 (6): 1150–1156. December 1997. doi:10.1124/mol.52.6.1150. PMID 9396785. 
  7. ↑ "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. June 1997. doi:10.1016/S0014-2999(97)89186-8. PMID 9226420. 

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See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

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