gb-115 and Inflammation

Anti-inflammatory effects of GB-115 compound (N-phenylhexanoyl-glycyl-L-tryptophan amide) injected intraperitoneally in doses of 0.1, 1, and 10 mg/kg were demonstrated on the model of ConA- and carrageenan-induced inflammation. Intraperitoneal injection of GB-115 in a dose of 1 mg/kg to C57Bl/6 female mice with experimental autoimmune encephalomyelitis significantly alleviated the pathological symptoms, improved spontaneous locomotor activity, promoted recovery of thymus weight, and reduced edema and neutrophil infiltration of the perivascular space of the brain tissue. Intraperitoneal injection of GB-115 in a dose of 1 mg/kg suppressed generation of active oxygen forms by neutrophils in the chemiluminescence test.

Topics: Animals; Anti-Inflammatory Agents; Brain; Carrageenan; Cholecystokinin; Concanavalin A; Dipeptides; Encephalomyelitis, Autoimmune, Experimental; Female; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Neutrophil Infiltration; Neutrophils; Rats; Reactive Oxygen Species; Thymus Gland

Preclinical safety investigations of newly synthesized dipeptide compound GB-115 (amide N-phenylhexanoyl-glycyl-L-tryptophan), an antagonist of cholecystokinin receptors, were performed. No animals were lost after GB-115 acute oral administration at a maximum dose of 6000 mg/kg in mice and at 3500 mg/kg in rats. GB-115 administered per os during 6 months in rabbits and rats (both males and females) at the doses of 0.1 and 10 mg/kg induced no irreversible pathological changes in organs and systems studied. The tested dipeptide exhibited no allergenic, immunotoxic and mutagenic activity, and did not affect generative function and the antenatal and postnatal development of progeny. GB-115 at a dose of 10 mg/kg produced suppression of the inflammatory reaction to concanavalin A.

Topics: Animals; Concanavalin A; Dipeptides; Drug Evaluation, Preclinical; Female; Guinea Pigs; Inflammation; Male; Mice; Rabbits; Rats; Receptors, Cholecystokinin