GML-1 is a TSPO (peripheral benzodiazepine receptor) ligand with

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

activity. 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 GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on ...

). The compound GML-1 was the most active of a series of 1-arylpyrrolo ,2-ayrazine-3-carboxamides, and its anxiolytic effects were examined using the

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test (OFT) and the

elevated plus maze The elevated plus maze (EPM) is a test measuring anxiety in laboratory animals that usually uses rodents as a screening test for putative anxiolytic or anxiogenic compounds and as a general research tool in neurobiological anxiety research su ...

(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. The TSPO-mechanism of anxiolytic action of GML-1 was proved by inhibitor analysis with TSPO antagonist PK11195 that blocks effect of GML-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

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and

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. 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.

References

Anxiolytics TSPO ligands {{Anxiolytic-stub