GML-1

{{Short description|Chemical compound}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 451564612

| IUPAC_name = N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide

| image = GML-1 structure.svg

| width = 177

| PubChem = 122393153

| ChemSpiderID = 67166536

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 1772608-75-9

| C=22 | H=19 | N=3 | O=1

| StdInChI=1S/C22H19N3O/c1-24(15-17-9-4-2-5-10-17)22(26)19-16-25-14-8-13-20(25)21(23-19)18-11-6-3-7-12-18/h2-14,16H,15H2,1H3

| StdInChIKey = QFYYHTVZHIEVCW-UHFFFAOYSA-N

| SMILES = CN(CC1=CC=CC=C1)C(=O)C2=CN3C=CC=C3C(=N2)C4=CC=CC=C4

}}

GML-1 is a TSPO (peripheral benzodiazepine receptor) ligand with anxiolytic activity.{{cite journal |vauthors=Mokrov GV, Deeva OA, Gudasheva TA, Yarkov SA, Yarkova MA, Seredenin SB |title=Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides |journal=Bioorganic & Medicinal Chemistry |volume=23 |issue=13 |pages=3368–78 |date=Jul 2015 |pmid=25937237 |doi= 10.1016/j.bmc.2015.04.049}} 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.

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 trilostane and finasteride.{{cite journal |vauthors=Yarkova MA, Mokrov GV, Gudasheva TA, Seredenin SB |title=Novel Pyrrolo[1,2-a]Pyrazines (TSPO Ligands) with Anxiolytic Activity Dependent on Neurosteroid Biosynthesis |journal=Pharmaceutical Chemistry Journal |volume=50 |issue=8 |pages=501–4 |date=Nov 2016 |doi= 10.1007/s11094-016-1476-0|s2cid=35338758 }}

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.{{cite journal |vauthors=Yarkova MA, Blynskaya EV, Yudina DV, Mokrov GV, Gudasheva TA, Alekseev KV |title=Development and Study of Anxiolytic Effect of GML-1 Tablet Dosage Form |journal=Pharmaceutical Chemistry Journal |volume=53 |issue=4 |pages=342–346 |date=Jul 2019 |doi= 10.1007/s11094-019-02003-1|s2cid=195878442 }}