From Wikipedia, the free encyclopedia
Benzodiazepine drug
GL-II-73
(4R)-8-ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide
PubChem
CID
Formula C 23 H 19 F N 4 O
Molar mass 386.430 g·mol−1 3D model (
JSmol )
CN(C)C(=O)c4ncn2c4[C@@H](C)N=C(c1cc(C#C)ccc12)c3ccccc3F
InChI=1S/C23H19FN4O/c1-5-15-10-11-19-17(12-15)20(16-8-6-7-9-18(16)24)26-14(2)22-21(23(29)27(3)4)25-13-28(19)22/h1,6-14H,2-4H3/t14-/m1/s1
Key:LNPOWXXHIUMIKI-CQSZACIVSA-N
GL-II-73 (GL-ii-073 ) is a
benzodiazepine derivative related in chemical structure to compounds such as
midazolam and
adinazolam . It is described as an α5 preferring
positive allosteric modulator of the benzodiazepine site of
GABAA receptors , with weaker activity at α2 and α3 and no significant affinity for the α1 subtype. In animal tests it was found to produce effects consistent with
antidepressant ,
anxiolytic and
nootropic actions.
[1]
[2]
[3]
[4]
[5]
[6]
[7]
See also
References
^
CA 3016491 , 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.", published 21 September 2017, assigned to Centre for Addiction and Mental Health, Faculty Of Pharmacy, University of Belgrade and UWM Res Foundation Inc
^ Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE, Stephen MR, Kodali R, Zahn NM, Arnold LA (January 2018).
"Potential combined pro-cognitive, anxiolytic and antidepressant properties of novel GABAA receptor positive modulators with preferential efficacy at the α5-subunit" (PDF) . bioRxiv : 332908.
doi :
10.1101/332908 .
S2CID
90987308 .
^ 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 (April 2019).
"Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles" . Molecular Neuropsychiatry . 5 (2): 84–97.
doi :
10.1159/000496086 .
PMC
6528097 .
PMID
31192221 .
^ Sibille E (February 2019).
"Brain Inhibitory GABAergic Function and Cognitive Deficits: Mechanisms and Therapeutic Targeting" (PDF) . Presentation for AAAS . Archived from
the original (PDF) on 2019-04-12. Retrieved 2019-03-09 .
^ Maramai S, Benchekroun M, Ward SE, Atack JR (April 2020).
"Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABAA R) Modulators Acting at the Benzodiazepine Binding Site: An Update" . Journal of Medicinal Chemistry . 63 (7): 3425–3446.
doi :
10.1021/acs.jmedchem.9b01312 .
PMID
31738537 .
S2CID
208171129 .
^ Bernardo A, Lee P, Marcotte M, Mian MY, Rezvanian S, Sharmin D, Kovačević A, Savić MM, Cook JM, Sibille E, Prevot TD (August 2022).
"Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress" . Neuropsychopharmacology . 47 (9): 1608–1619.
doi :
10.1038/s41386-022-01360-y .
PMC
9283409 .
PMID
35701547 .
^ Perez SM, McCoy AM, Prevot TD, Mian MY, Carreno FR, Frazer A, Cook JM, Sibille E, Lodge DJ (January 2023).
"Hippocampal α5-GABAA Receptors Modulate Dopamine Neuron Activity in the Rat Ventral Tegmental Area" . Biological Psychiatry Global Open Science . 3 (1): 78–86.
doi :
10.1016/j.bpsgos.2021.12.010 .
PMC
9874136 .
PMID
36712569 .
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