Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and QH-II-66: Difference between pages

{{Short description|Benzodiazepine sedative drug}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 464378091

| image = QH-II-66.svg

| width = 200

| legal_CA = Schedule IV

| legal_UK = PSA

| legal_DE = NpSG

| legal_status =

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 183239-39-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = PKW6UCK55B

| smiles = O=C1N(C)C2=C(C(C3=CC=CC=C3)=NC1)C=C(C=C2)C#C

'''QH-II-66'''<ref>{{cite patent | country = US | number = 2010004226 | title = Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects | inventor = Cook JM, Hao H, Huang S, Sarma PV, Zhang C | pubdate = 7 January 2010 }}</ref> (QH-ii-066) is a [[sedative]] drug which is a [[benzodiazepine]] derivative.<ref name="pmid10633039">{{cite journal | vauthors = Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM | display-authors = 6 | title = Pharmacophore/receptor models for GABA_A/BzR subtypes (α₁β₃γ₂, α₅β₃γ₂, and α₆β₃γ₂) via a comprehensive ligand-mapping approach | journal = Journal of Medicinal Chemistry | volume = 43 | issue = 1 | pages = 71–95 | date = January 2000 | pmid = 10633039 | doi = 10.1021/jm990341r }}</ref> It produces some of the same effects as other benzodiazepines, but is much more selective than most other drugs of this class and so produces somewhat less sedation and [[ataxia]] than other related drugs such as [[diazepam]] and [[triazolam]], although it still retains [[anticonvulsant]] effects.<ref>{{cite patent | country = US | number = 7119196 | title = Anxiolytic agents with reduced sedative and ataxic effects | inventor = Cook JM, Huang Q, He X, Li X, Yu J, Han D, Lelas S, McElroy JF | assign1 = WiSys Technology Foundation Inc | gdate = 10 September 2006 }}</ref>

QH-ii-066 is a highly subtype-selective [[GABAA receptor|GABA_A]] [[agonist]] which was designed to bind selectively to the [[GABRA5|α₅ subtype]] of GABA_A receptors.<ref>{{cite journal | vauthors = Huang Q, Zhang W, Liu R, McKernan RM, Cook JM | title = Benzo-fused benzodiazepines employed as topological probes for the study of benzodiazepine receptor subtypes | journal = Medicinal Chemistry Research | volume = 6 | issue = 3 | pages = 384–391 | year = 1996 }}</ref>

The α₅ subtype (and to a lesser extent the α₁ subtype) of GABA_A are two of the most important targets in the brain that produce the effects of [[Alcoholic beverage|alcohol]],<ref name="pmid15650112">{{cite journal | vauthors = Platt DM, Duggan A, Spealman RD, Cook JM, Li X, Yin W, Rowlett JK | title = Contribution of alpha 1GABAA and alpha 5GABAA receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 313 | issue = 2 | pages = 658–67 | date = May 2005 | pmid = 15650112 | doi = 10.1124/jpet.104.080275 | s2cid = 97681615 }}</ref> and so one of the purposes for which QH-ii-066 was developed was to reproduce the [[Gamma-aminobutyric acid|GABAergic]] effects of alcohol separately from its other actions.<ref name="pmid16441269">{{cite journal | vauthors = Hodge CW, Grant KA, Becker HC, Besheer J, Crissman AM, Platt DM, Shannon EE, Shelton KL | display-authors = 6 | title = Understanding how the brain perceives alcohol: neurobiological basis of ethanol discrimination | journal = Alcoholism: Clinical and Experimental Research | volume = 30 | issue = 2 | pages = 203–13 | date = February 2006 | pmid = 16441269 | doi = 10.1111/j.1530-0277.2006.00024.x }}</ref>

QH-ii-066 replicates some of the effects of alcohol, such as sedation and ataxia, but does not increase appetite, as this effect seems to be produced by the α₁ subtype of GABA_A rather than α₅.<ref name="pmid16783540">{{cite journal | vauthors = Duke AN, Platt DM, Cook JM, Huang S, Yin W, Mattingly BA, Rowlett JK | title = Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABAA receptor subtypes | journal = Psychopharmacology | volume = 187 | issue = 3 | pages = 321–30 | date = August 2006 | pmid = 16783540 | doi = 10.1007/s00213-006-0431-2 | s2cid = 32950492 }}</ref> The [[inverse agonist]] [[Ro15-4513]], which blocks the α₅ subtype of GABA_A, reverses the effects of alcohol, suggesting that this subtype is also important in producing the subjective effects of alcohol intoxication.<ref name="pmid16698930">{{cite journal | vauthors = Wallner M, Hanchar HJ, Olsen RW | title = Low-dose alcohol actions on alpha4beta3delta GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 22 | pages = 8540–5 | date = May 2006 | pmid = 16698930 | pmc = 1482527 | doi = 10.1073/pnas.0600194103 | bibcode = 2006PNAS..103.8540W | doi-access = free }}</ref>

== See also ==

* [[GL-II-73]]

* [[Pyeazolam]]

* [[SH-I-048A]]

* [[SH-053-R-CH3-2′F]]

== References ==

{{Reflist}}

{{Benzodiazepines}}

{{Hypnotics and sedatives}}

{{GABAAR PAMs}}

[[Category:Benzodiazepines]]

[[Category:Sedatives]]

[[Category:Hypnotics]]

[[Category:Ethynyl compounds]]

[[Category:Lactams]]

{{sedative-stub}}