GB-115

GB-115 is N-(6-phenylhexanoyl)glycyl-L-tryptophan amide, a dipeptide analog of the endogenous tetrapeptide cholecystokinin-4 (CCK-4). It was designed at the V. V. Zakusov Institute of Pharmacology in Moscow as part of a dipeptide drug program that also produced Noopept (Gudasheva et al., 2018). In the series that yielded it, L-tryptophan analogs had anxiolytic-like activity in rats and D-tryptophan analogs anxiogenic activity, and GB-115 was chosen for further study (Gudasheva et al., 2007).

Its developers describe it as a retro analog of CCK-4 (Kolik et al., 2012) and an antagonist of central cholecystokinin receptors (Kolik et al., 2003).

Confirm the spray's solvent before solvent-sensitive work.

Published work on GB-115 falls into six areas. Apart from one study in rhesus monkeys, one small clinical study and a preclinical safety study that also used rabbits (Sorokina et al., 2010), the evidence comes from rodents, and nearly all of it comes from the developing institute.

Design and structure

GB-115 came from a series with the general formula Ph(CH₂)ₙCO-NH(CH₂)ₘCO-Trp-NH₂, built on the structure of CCK-4 (Gudasheva et al., 2007). Proton NMR in solution and a set of sterically restricted analogs pointed to a beta-II turn as its biologically active conformation (Gudasheva et al., 2013). A review from the institute describes its design approach, built around the beta-turn of regulatory peptides, and calls GB-115 a tripeptoid analog of CCK-4 (Gudasheva et al., 2018). Models: chemical synthesis, NMR and rat behavior.

Anxiety tests and stress phenotype

Effects depended on how the animals respond to stress. GB-115 increased open-field activity in BALB/c mice but not C57Bl/6 mice, and it was anxiolytic-like in MR rats but not MNRA rats in elevated plus-maze and conflict tests (Kolik et al., 2003).

Activating CCK2 receptors abolished its effect in BALB/c mice, and it prevented anxiety induced by CCK-4 but not by yohimbine, which the authors read as GB-115 and CCK-4 sharing a target (Kolik et al., 2012). Active amounts moved from 0.006 to 0.1 mg/kg given intraperitoneally to 0.1 to 5.0 mg/kg by mouth (Kolik et al., 2013). Models: inbred and outbred mice and rats.

Tolerance, withdrawal and alcohol models

Rats that received GB-115 at 0.1 mg/kg intraperitoneally each day for 30 days kept the anxiolytic-like response, and stopping it produced no behavioral or convulsive withdrawal signs; stopping diazepam after the same period raised anxiety, lowered the aggression threshold and increased convulsive readiness (Kolik et al., 2011). In MR rats with 12 months of free access to ethanol, GB-115 at 0.025 mg/kg intraperitoneally for 14 days significantly reduced average daily ethanol consumption and the alcohol-deprivation effect, with no such change in MNRA rats (Kolik et al., 2016). Models: outbred and selectively bred rats.

Pain models and opioid interactions

In outbred mice, GB-115 strengthened morphine analgesia in the hot-plate test, a naloxone-sensitive effect, but did not change behavior in the tail-flick test (Kolik et al., 2007). Given by mouth at 0.1 to 20 mg/kg, it reduced acetic acid-induced abdominal contractions to a degree comparable with diclofenac at 20 mg/kg, and naloxone only partly reversed this, which the authors read as a significant non-opioid component (Kolik et al., 2012). Model: mice.

Inflammation and pharmacokinetics

Intraperitoneal GB-115 at 0.1 to 10 mg/kg reduced concanavalin A- and carrageenan-induced inflammation, and at 1 mg/kg it reduced clinical signs, brain edema and perivascular neutrophil infiltration in female C57Bl/6 mice with experimental autoimmune encephalomyelitis (Shipaeva et al., 2011). Pharmacokinetic work by HPLC found GB-115 resistant to peptidases, with an absolute oral bioavailability of 4.65% (Boyko et al., 2007). Models: mice with encephalomyelitis, plus inflammation and pharmacokinetic models whose species the abstracts do not name.

Primate and human studies

In four male rhesus monkeys housed individually, GB-115 tablets given by mouth for two 7-day periods reduced time spent in the upper part of the cage, which the authors read as a lower stress response, and the higher amount lowered the cortisol to DHEA-S ratio; phenazepam had comparable behavioral effects (Panchenko et al., 2025).

In a 2019 clinical study from the institute, 31 adults with generalized anxiety disorder received GB-115 tablets for 21 days, and the authors reported a fast-onset anxiolytic effect and good tolerability; the abstract does not mention a placebo or comparator group (Neznamov et al., 2019). Models: rhesus monkeys; adults with generalized anxiety disorder.