Evaluation of allergenic properties and immunotoxicity tablet dosage form GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazin-3-carboxamide)

The study of allergenic properties and immunotoxic effects of the ready-to-use drug form of GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazin-3-carboxamide), compounds with high TSPO affinity and pronounced anxiolytic activity, was carried out. The study of allergenic properties and immunotoxicity of GML-1 was performed on male albino guinea pigs weighing 250-300 g and on male CBA, C57BL / 6, F1 hybrids (CBAxC57BL/6) mice. When assessing immunotoxicity, GML-1 was inject to mice per os for 14 days in doses of 2.2 mg / kg and 22 mg / kg. When studying the allergenicity, GML-1 was injected to albino guinea pigs in doses of 1 mg / kg and 10 mg / kg according to standard regimens of immunization. The results of the study of the immuno-toxicity and allergenicity of GML-1 allow us to conclude that the injection of tablet dosage form of GML-1 in the range of studied doses does not have an immunotoxic effect and allergenic properties.

tablet dosage form of GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1, 2-a]pyrazin-3-carboxamide), phagocytosis, chemiluminescence, humoral immune response, cellular immune response, immunotoxicity, systemic anaphylaxis, delayed hypersensitivity, concanavalin A-induced inflammation

1. Yarkova MA, Mokrov GV, Gudasheva TA, Seredenin SB. Molecularbiological problems of drug design and mechanism of drug action: novel pyrrolo[1,2-A]pyrazines (tspo ligands) with anxiolytic activity dependent on neurosteroid biosynthesis. Pharmaceutical Chemistry Journal. 2016;50(8): 3–6. (In Russ).

2. Yarkova MA, Litvin AA, Kolyvanov GB, Zherdev VP, Seredenin SB, Gegechkori VI. Search of the correlation between anxiolytic effect of original derivative of pyrrolo[1,2-a]pyrazine TSPO-ligand (GML-1) and its concentrations in the rat blood plasma. Farmakokinetika i farmakodinamika. 2018;(2):52–58. (In Russ). DOI: 10.24411/2587-7836-2018-10014

3. Kovalenko LP, Fedoseeva VN, Durnev AD, et al. Metodicheskie recomendacii po otsenke allergiziruushchih svoistv lekarstvennih sredstv. Rukovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Ch.1. Moscow: Grif i K, 2012; Ch.2:51–63. (In Russ).

4. Haitov RM, Ivanova AS, Kovalenko LP, et al. Metodicheskie recomendacii po otsenke immunotoksicheskogo deistviia farma-kologicheskih veshchestv. Rukovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Ch.1. Moscow: Grif i K, 2012; Ch.3:64–79. (In Russ).

5. Haitov RM, Gushchin IS, Pinegin BV, et al. Metodicheskie recomendacii po doklinicheskomu izucheniiu immunotropnoi aktivnosti farmakologicheskih veshchestv. Rukovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Ch.1. Moscow: Grif i K. 2012; Ch.38:624–639. (In Russ).