GB-115

Also known as: Ranquilon, L-Tryptophanamide, N-(1-oxo-6-phenylhexyl)glycyl-, N-6-Phenylhexanoyl-glycyl-L-tryptophan, N-(1-Oxo-6-phenylhexyl)glycyl-L-tryptophanamide, N-phenylhexanoyl-glycyl-L-tryptophan amide
Retroanalogue of cholecystokinin-4 (CCK-4).
Research indicates GB-115 has significant anxiolytic properties, making it a candidate for treating generalized anxiety disorder (GAD). A clinical study involving 31 patients with GAD, diagnosed per ICD-10 (F41.1), determined an effective dose of 6 mg per day. The treatment, administered over 21 days, was associated with a fast onset of anxiolytic effects, beneficial impacts on sleep disturbances, and improvements in autonomic symptoms. Additionally, it favorably altered attention parameters, suggesting cognitive benefits alongside anxiety reduction.
In preclinical models, GB-115 demonstrated anxiolytic effects in behavioral tests. For instance, in outbred mice, doses ranging from 0.1 to 0.5 mg/kg were effective in the open field test, while in inbred BALB/c mice, doses of 0.1 and 5.0 mg/kg showed efficacy. In the elevated plus-maze test, a standard measure of anxiety, GB-115 increased the time spent in open arms in outbred rats at 0.5-0.7 mg/kg and in BALB/c mice at 0.1 mg/kg, indicating reduced anxiety-like behavior (source).
Further, a study on pharmaceutical compositions of GB-115 found that a controlled-release formulation (composition 4) increased residence time in the elevated plus-maze open arms at doses of 0.3 mg/kg and 0.9 mg/kg (p < 0.01) compared to placebo, highlighting its potential for optimized delivery (source).
GB-115’s impact on cognitive functions is notable, particularly in GAD patients. A study with 25 patients (mean age 35.76 ± 8.55 years) treated with 6 mg/day for 21 days reported significant improvements in cognitive metrics (source). The results, summarized in the table below, show enhancements in reaction time, attention parameters, and performance in the Shulte-Platonov tables test:

Measure	Background	Day 3	Day 7	Day 14	Day 21	% Improvement (Day 21 vs Background)
Reaction Time (msec)	449.19±64.91	-	418.17±61.49*	422.25±70.69*	406.5±52.79*	9.5%
Attention Parameters (msec)	316.41±42.35	305.95±45.31*	-	-	300.14±47.74*	5.14%
Shulte-Platonov Tables (sec)	68.84±16.78	-	59.40±13.71*	57.88±12.82*	53.40±13.19*	22.4%

(*p≤0.01 for reaction time and Shulte-Platonov on Days 7, 14, 21; p≤0.05 for attention parameters on Days 3, 21 compared to background). These improvements suggest GB-115 not only mitigates anxiety but also enhances cognitive processing, potentially benefiting patients with GAD-related cognitive deficits.
GB-115 exhibits immunocorrecting properties, particularly in animal models. In intact mice, doses of 0.1–10 mg/kg stimulated phagocytic activity of peritoneal macrophages and enhanced humoral immune responses. In mice with secondary immunodeficiency induced by cyclophosphamide, GB-115 demonstrated activity in restoring immune function, suggesting potential applications in conditions involving immune dysregulation (source).
The anti-inflammatory actions of GB-115 are evident in preclinical models. In studies using ConA- and carrageenan-induced inflammation, intraperitoneal injections at doses of 0.1, 1, and 10 mg/kg reduced inflammatory responses. Notably, at 1 mg/kg, GB-115 alleviated symptoms in a model of experimental autoimmune encephalomyelitis, improving spontaneous locomotor activity, promoting recovery of thymus weight, and reducing edema and neutrophil infiltration in brain tissue. It also suppressed the generation of active oxygen forms by neutrophils, as measured by chemiluminescence, indicating a role in mitigating oxidative stress-related inflammation (source).
GB-115’s interaction with pain pathways is complex, involving opioidergic systems. In mice, it potentiated morphine-induced analgesia in the hot-plate test, an effect that was naloxone-dependent, suggesting involvement with opioid receptors. However, it did not modulate behavior in the tail-flick test, indicating specificity to certain pain modalities, likely supraspinal mechanisms. Further, research suggests GB-115 (4 mg/kg) increases response latency in the hot-plate test in a naloxone-independent manner, while producing a moderate naloxone-reversible effect in the tail-flick test, pointing to spinal-level opioidergic interactions (source1 and source2).
The primary mechanism of GB-115 involves antagonism of CCK2 receptors, which are critical in anxiety and pain modulation.
GB-115 is under investigation in clinical trials for anxiety in neurasthenia and adjustment disorders, suggesting broader applications beyond GAD. Its ability to improve cognitive functions, modulate immune responses, and reduce inflammation positions it as a candidate for conditions involving these systems (source).