SH-053-R-CH3-2′F explained

SH-053-R-CH3-2′F is a drug used in scientific research which is a benzodiazepine derivative. It produces some of the same effects as other benzodiazepines, but is much more subtype-selective than most other drugs of this class, having high selectivity, binding affinity and efficacy at the α₅ subtype of the GABA_A receptor. This gives much tighter control of the effects produced, and so while SH-053-R-CH3-2′F retains sedative and anxiolytic effects, it does not cause ataxia at moderate doses.^[1] SH-053-R-CH3-2′F also blocks the nootropic effects of the α₅-selective inverse agonist PWZ-029, so amnesia is also a likely side effect.^[2]

Replacement of the ester function by an amide, realized in analogs such as MP-III-022 and GL-II-73, improves selectivity, efficacy, and kinetic behavior.^{[3] [4] [5]}

See also

• Pyeazolam
• QH-ii-066
• SH-I-048A

Notes and References

1. Savić MM, Huang S, Furtmüller R, Clayton T, Huck S, Obradović DI, Ugresić ND, Sieghart W, Bokonjić DR, Cook JM . 6 . Are GABAA receptors containing alpha5 subunits contributing to the sedative properties of benzodiazepine site agonists? . Neuropsychopharmacology . 33 . 2 . 332–339 . January 2008 . 17392731 . 10.1038/sj.npp.1301403 . free .
2. Savić MM, Clayton T, Furtmüller R, Gavrilović I, Samardzić J, Savić S, Huck S, Sieghart W, Cook JM . 6 . PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats . Brain Research . 1208 . 150–159 . May 2008 . 18394590 . 2577822 . 10.1016/j.brainres.2008.02.020 .
3. Stamenić TT, Poe MM, Rehman S, Santrač A, Divović B, Scholze P, Ernst M, Cook JM, Savić MM . 6 . Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA_A receptors containing the α5 subunit . European Journal of Pharmacology . 791 . 433–443 . November 2016 . 27639297 . 5107132 . 10.1016/j.ejphar.2016.09.016 .
4. Cook JM, Li G, Poe M, Savic M, Sibille E . Treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders with alpha5-containing gabaa receptor agonists. . CA . 3016491 .
5. Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE, Stephen MR, Kodali R, Zahn NM, Arnold LA, Scholze P, Fisher JL, Marković BD, Banasr M, Cook JM, Savic M, Sibille E . 6 . Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles . Molecular Neuropsychiatry . 5 . 2 . 84–97 . April 2019 . 31192221 . 6528097 . 10.1159/000496086 .