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 anxie ...

activity. Its binding affinity (Ki value) to TSPO is comparable with

PK11195 PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high ...

. 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 o ...

). The compound GML-1 was the most active of a series of 1-arylpyrrolo

,2-a The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline o ...

yrazine-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 suc ...

(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

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

trilostane Trilostane, sold under the brand names Modrenal and Vetoryl among others, is a medication which has been used in the treatment of Cushing's syndrome, Conn's syndrome, and postmenopausal breast cancer in humans. It was withdrawn for use in humans ...

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