{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = Thio-THIP.svg | image_class = skin-invert-image | width = 175px | caption =
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = GABA<sub>A</sub> receptor weak partial agonist or antagonist; GABA<sub>A</sub>-ρ receptor antagonist; GABA reuptake inhibitor | ATC_prefix = None | ATC_suffix =
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<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 97164-95-9 | CAS_supplemental = | PubChem = 656720 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = 571058 | UNII = | KEGG = C13711 | ChEBI = 35010 | ChEMBL = 170539 | NIAID_ChemDB = | PDB_ligand = | synonyms = 4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol; Thiogaboxadol
<!-- Chemical data --> | IUPAC_name = 4,5,6,7-tetrahydro-[1,2]thiazolo[5,4-c]pyridin-3-one | C=6 | H=8 | N=2 | O=1 | S=1 | SMILES = C1CNCC2=C1C(=O)NS2 | StdInChI = 1S/C6H8N2OS/c9-6-4-1-2-7-3-5(4)10-8-6/h7H,1-3H2,(H,8,9) | StdInChIKey = DZYJTJJQGHXSFN-UHFFFAOYSA-N }}
'''Thio-THIP''', also known as '''4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol''', is a low-potency GABA<sub>A</sub> receptor very weak partial agonist or antagonist related to gaboxadol (THIP).<ref name="KrogsgaardLarsen_2002">{{cite journal | vauthors = Krogsgaard-Larsen P, Frølund B, Liljefors T | title = Specific GABA(A) agonists and partial agonists | journal = Chemical Record | volume = 2 | issue = 6 | pages = 419–430 | date = 2002 | pmid = 12469353 | doi = 10.1002/tcr.10040 }}</ref><ref name="KrogsgaardLarsen_2006">{{cite book | vauthors = Krogsgaard-Larsen P, Frølund B, Liljefors T | title = GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic | chapter = GABAA Agonists and Partial Agonists: THIP (Gaboxadol) as a Non-Opioid Analgesic and a Novel Type of Hypnotic1 | series = Advances in Pharmacology | volume = 54 | pages = 53–71 | date = 2006 | pmid = 17175810 | doi = 10.1016/s1054-3589(06)54003-7 | isbn = 978-0-12-032957-1 }}</ref><ref name="Brehm_1997">{{cite journal | vauthors = Brehm L, Ebert B, Kristiansen U, Wafford K, Kemp J, Krogsgaard-Larsen P | title = Structure and pharmacology of 4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol (Thio-THIP), an agonist/antagonist at GABAA receptors | journal = European Journal of Medicinal Chemistry | volume = 32 | issue = 4 | pages = 357–363 | date = 1997 | doi = 10.1016/S0223-5234(97)89089-7 | url = https://linkinghub.elsevier.com/retrieve/pii/S0223523497890897 | access-date = 5 October 2025 | url-access = subscription }}</ref> It is also a weak GABA<sub>A</sub>-ρ receptor antagonist<ref name="Frlund_2002">{{cite journal | vauthors = Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P | title = GABA(A) receptor ligands and their therapeutic potentials | journal = Current Topics in Medicinal Chemistry | volume = 2 | issue = 8 | pages = 817–832 | date = August 2002 | pmid = 12171573 | doi = 10.2174/1568026023393525 }}</ref><ref name="Krehan_2003">{{cite journal | vauthors = Krehan D, Frølund B, Ebert B, Nielsen B, Krogsgaard-Larsen P, Johnston GA, Chebib M | title = Aza-THIP and related analogues of THIP as GABA C antagonists | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 23 | pages = 4891–4896 | date = November 2003 | pmid = 14604650 | doi = 10.1016/j.bmc.2003.09.016 }}</ref> and a weak GABA reuptake inhibitor.<ref name="KrogsgaardLarsen_2006" /> The drug has three orders of magnitude lower potency as a GABA<sub>A</sub> receptor modulator than gaboxadol.<ref name="KrogsgaardLarsen_1981" /><ref name="KrogsgaardLarsen_1983" /> This is unlike the case of muscimol and thiomuscimol, which are almost equipotent.<ref name="KrogsgaardLarsen_1994">{{cite journal | vauthors = Krogsgaard-Larsen P, Frølund B, Jørgensen FS, Schousboe A | title = GABAA receptor agonists, partial agonists, and antagonists. Design and therapeutic prospects | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 16 | pages = 2489–2505 | date = August 1994 | pmid = 8057295 | doi = 10.1021/jm00042a001 }}</ref> Like gaboxadol, thio-THIP is a zwitterion.<ref name="KrogsgaardLarsen_2002" /><ref name="KrogsgaardLarsen_1994" /> It may cross the blood–brain barrier similarly to gaboxadol.<ref name="KrogsgaardLarsen_1994" /> Thio-THIP was developed and described by Povl Krogsgaard-Larsen and colleagues by 1981.<ref name="KrogsgaardLarsen_1981">{{cite journal | vauthors = Krogsgaard-Larsen P, Brehm L, Schaumburg K | title = Muscimol, a psychoactive constituent of Amanita muscaria, as a medicinal chemical model structure | journal = Acta Chemica Scandinavica B | volume = 35 | issue = 5 | pages = 311–324 | date = 1981 | pmid = 6274117 | doi = 10.3891/acta.chem.scand.35b-0311 }}</ref><ref name="KrogsgaardLarsen_1981a">{{cite journal | vauthors = Krogsgaard-Larsen P | title = gamma-Aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects | journal = Journal of Medicinal Chemistry | volume = 24 | issue = 12 | pages = 1377–1383 | date = December 1981 | pmid = 6118436 | doi = 10.1021/jm00144a001 }}</ref><ref name="KrogsgaardLarsen_1983">{{cite journal | vauthors = Krogsgaard-Larsen P, Mikkelsen H, Jacobsen P, Falch E, Curtis DR, Peet MJ, Leah JD | title = 4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogues of THIP. Synthesis and biological activity | journal = Journal of Medicinal Chemistry | volume = 26 | issue = 6 | pages = 895–900 | date = June 1983 | pmid = 6304315 | doi = 10.1021/jm00360a020 }}</ref>
== See also == * Aza-THIP * Iso-THIP * THAZ * THPO * 4-PIOL * Thio-4-PIOL
== References == {{Reflist}}
{{GABA receptor modulators}} {{GABA metabolism and transport modulators}}
Category:GABA analogues Category:GABA reuptake inhibitors Category:GABAA receptor agonists Category:GABAA receptor antagonists Category:GABAA-rho receptor antagonists Category:Isothiazoles Category:Ketones Category:Zwitterions
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