GML-1 is a TSPO (peripheral benzodiazepine receptor) ligand with anxiolytic activity.[1] Its binding affinity (Ki value) to TSPO is comparable with PK11195. GML-1 is selective for TSPO versus the central benzodiazepine receptor (CBR, GABAA receptor). The compound GML-1 was the most active of a series of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides, and its anxiolytic effects were examined using the open field test (OFT) and the elevated plus maze (EPM) test. The EPM test is a general anxiety test measuring the time spent by animals in the open or the enclosed arms. When compound was administered to CD-1 mice at the dose of 1.0 mg/kg, it significantly increased the percentage of open arm entries and the time spent in the open arms. GML-1 is a potential antianxiety agent.
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| Formula | C22H19N3O |
| Molar mass | 341.414 g·mol−1 |
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The TSPO-mechanism of anxiolytic action of GML-1 was proved by inhibitor analysis with TSPO antagonist PK11195 that blocks effect of GML-1.[1]
The involvement of neurosteroids in the mechanism of action of GML-1 was confirmed by co-administration of GML-1 with neurosteroid synthesis inhibitors. The anxiolytic effect of GML-1 in elevated plus-maze tests was completely blocked by the neurosteroidogenic-enzyme inhibitors trilostane and finasteride.[2]
The tablet dosage form of GML-1 was developed and showed pronounced anxiolytic activity after intragastric administration in rats in a wide range of doses.[3]
References
edit- ^ a b Mokrov GV, Deeva OA, Gudasheva TA, Yarkov SA, Yarkova MA, Seredenin SB (Jul 2015). "Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides". Bioorganic & Medicinal Chemistry. 23 (13): 3368–78. doi:10.1016/j.bmc.2015.04.049. PMID 25937237.3368-78&rft.date=2015-07&rft_id=info:doi/10.1016/j.bmc.2015.04.049&rft_id=info:pmid/25937237&rft.aulast=Mokrov&rft.aufirst=GV&rft.au=Deeva, OA&rft.au=Gudasheva, TA&rft.au=Yarkov, SA&rft.au=Yarkova, MA&rft.au=Seredenin, SB&rfr_id=info:sid/en.wikipedia.org:GML-1" class="Z3988">
- ^ Yarkova MA, Mokrov GV, Gudasheva TA, Seredenin SB (Nov 2016). "Novel Pyrrolo[1,2-a]Pyrazines (TSPO Ligands) with Anxiolytic Activity Dependent on Neurosteroid Biosynthesis". Pharmaceutical Chemistry Journal. 50 (8): 501–4. doi:10.1007/s11094-016-1476-0. S2CID 35338758.501-4&rft.date=2016-11&rft_id=info:doi/10.1007/s11094-016-1476-0&rft_id=https://api.semanticscholar.org/CorpusID:35338758#id-name=S2CID&rft.aulast=Yarkova&rft.aufirst=MA&rft.au=Mokrov, GV&rft.au=Gudasheva, TA&rft.au=Seredenin, SB&rfr_id=info:sid/en.wikipedia.org:GML-1" class="Z3988">
- ^ Yarkova MA, Blynskaya EV, Yudina DV, Mokrov GV, Gudasheva TA, Alekseev KV (Jul 2019). "Development and Study of Anxiolytic Effect of GML-1 Tablet Dosage Form". Pharmaceutical Chemistry Journal. 53 (4): 342–346. doi:10.1007/s11094-019-02003-1. S2CID 195878442.342-346&rft.date=2019-07&rft_id=info:doi/10.1007/s11094-019-02003-1&rft_id=https://api.semanticscholar.org/CorpusID:195878442#id-name=S2CID&rft.aulast=Yarkova&rft.aufirst=MA&rft.au=Blynskaya, EV&rft.au=Yudina, DV&rft.au=Mokrov, GV&rft.au=Gudasheva, TA&rft.au=Alekseev, KV&rfr_id=info:sid/en.wikipedia.org:GML-1" class="Z3988">
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