QH-II-66 (QH-ii-066) is a sedative drug which is a benzodiazepine derivative. 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.
QH-ii-066 is a highly subtype-selective GABAA agonist which was designed to bind selectively to the α5 subtype of GABAA receptors.
The α5 subtype (and to a lesser extent the α1 subtype) of GABAA are two of the most important targets in the brain that produce the effects of alcohol, and so one of the purposes for which QH-ii-066 was developed was to reproduce the GABAergic effects of alcohol separately from its other actions.
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 GABAA rather than α5. It is also interesting to note that the inverse agonist Ro15-4513, which blocks the α4 subtype of GABAA, reverses the effects of alcohol, suggesting that this subtype is also important in producing the subjective effects of alcohol intoxication.
- ^ US Patent Application 2006/3995 A1 Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects
- ^ Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM (2000). "Pharmacophore/receptor models for GABAA/BzR subtypes (α1β3γ2, α5β3γ2, and α6β3γ2) via a comprehensive ligand-mapping approach". J. Med. Chem. 43 (1): 71–95. PMID 10633039. doi:10.1021/jm990341r.
- ^ James M. Cook, Qi Huang, Xiaohui He, Xioayan Li, Jianming Yu, Dongmei Han, Snjezana Lelas, John F. McElroy. US71191961
- ^ Huang Q, Zhang W, Liu R, McKernan RM, Cook JM (1996). "Benzo-fused benzodiazepines employed as topological probes for the study of benzodiazepine receptor subtypes". Medicinal Chemistry Research 6 (3): 384–391.
- ^ Platt DM, Duggan A, Spealman RD, Cook JM, Li X, Yin W, Rowlett JK (2005). "Contribution of α1 GABAA and α5 GABAA receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys". J. Pharmacol. Exp. Ther. 313 (2): 658–67. PMID 15650112. doi:10.1124/jpet.104.080275.
- ^ Hodge CW, Grant KA, Becker HC, Besheer J, Crissman AM, Platt DM, Shannon EE, Shelton KL (2006). "Understanding how the brain perceives alcohol: neurobiological basis of ethanol discrimination". Alcohol. Clin. Exp. Res. 30 (2): 203–13. PMID 16441269. doi:10.1111/j.1530-0277.2006.00024.x.
- ^ Duke AN, Platt DM, Cook JM, Huang S, Yin W, Mattingly BA, Rowlett JK (2006). "Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABAA receptor subtypes". Psychopharmacology (Berl.) 187 (3): 321–30. PMID 16783540. doi:10.1007/s00213-006-0431-2.
- ^ Wallner M, Hanchar HJ, Olsen RW (2006). "Low-dose alcohol actions on α4β3δ GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513". Proc. Natl. Acad. Sci. U.S.A. 103 (22): 8540–5. PMC 1482527. PMID 16698930. doi:10.1073/pnas.0600194103.
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