Description
Summary Abstract
GB-115 (N-(1-oxo-6-phenylhexyl)glycyl-L-tryptophanamide; Ranquilon; CAS 678996-63-9) is a synthetic dipeptidomimetic retroanalogue of cholecystokinin-4 (CCK-4) developed at the Serbsky National Medical Research Center (Moscow). Structurally composed of a 6-phenylhexanoyl chain linked to glycyl-L-tryptophanamide (molecular formula C25H30N4O3, MW 434.5 g/mol), it functions as a low-affinity antagonist at central cholecystokinin-1 (CCK1) and CCK2 receptors, modulating cholecystokinin (CCK)-mediated signaling in anxiety, stress response, and attentional circuits. A Phase 2 pilot clinical study demonstrated anxiolytic efficacy at 6 mg/day in patients with generalized anxiety disorder (GAD), with a favorable profile distinct from SSRIs — no initial overactivation, no sleep disruption onset, and positive effects on reaction time and cognitive performance. GB-115 is under investigation in NCT05586789 (Ranquilon tablets for anxiety in neurasthenia and adjustment disorders).
Clinical Indications
GB-115 has demonstrated activity across anxiety, cognitive, and neuroendocrine research paradigms:
- Generalized Anxiety Disorder (GAD): Phase 2 clinical trial: effective dose established at 6 mg/day; anxiolytic onset within initial treatment period; improved attention, reaction time, and operator performance without SSRI/SNRI-class activation side effects.
- Stress Response Modulation: Subchronic oral GB-115 in rhesus monkeys reduced cortisol/DHEA-S ratio and decreased stress-related cage behavior at 0.002 g/animal, with effects comparable to phenazepam, confirming translational activity in non-human primate models.
- CCK Receptor Pharmacology: Preclinical tool compound for dissecting CCK1/CCK2-mediated anxiety and antinociception pathways, including opioid-CCK interactions at spinal versus supraspinal levels.
Contraindications
- Phenotype-Specific Anxiety Models: GB-115 effects are phenotype-dependent — anxiolytic activity is documented in outbred rats and active-response BALB/c mice (C57Bl/6 background) but not in BALB/c mice exhibiting a freezing response to emotiogenic stimuli; model selection should account for this specificity.
- Yohimbine-Induced Anxiety Models: GB-115 does not prevent yohimbine (α2-adrenoceptor antagonist)-induced anxiety in C57Bl/6 mice, indicating the CCK1/CCK2 mechanism does not extend to noradrenergic anxiety pathways; appropriate control conditions are required in multi-pathway paradigms.
- Opioid Interaction Studies: The antinociceptive effects of GB-115 involve opioidergic mechanisms at the spinal level (naloxone-reversible in tail flick) but not supraspinal CCK2 pathways; mixed opioid-CCK study designs require careful dosing controls.
Mechanism of Action (MOA)
GB-115 engages central CCK receptor signaling through competitive antagonism at CCK1 and CCK2 subtypes:
CCK1 and CCK2 Receptor Antagonism
GB-115 functions as a low-affinity antagonist at central cholecystokinin-1 (CCK1) and CCK2 receptors, blocking endogenous CCK-4 and CCK-8 from driving anxiogenic signaling in limbic and cortical circuits. CCK receptor activation is implicated in panic, anxiety, and stress responses; its blockade reduces these behavioral endpoints in preclinical and clinical settings.
Dipeptidomimetic Retroanalogue Structure
The retroanalogue scaffold (reversed amide bonds relative to native CCK-4) confers metabolic stability against peptidase cleavage while maintaining receptor engagement geometry. This structural strategy, combined with the 6-phenylhexanoyl acyl chain and tryptamine pharmacophore, enables oral bioavailability with a CNS-penetrant pharmacokinetic profile documented in preclinical and clinical PK data.
Spinal Opioid Co-modulation
GB-115’s antinociceptive effects in the tail flick assay are naloxone-reversible, indicating opioid receptor involvement at the spinal level. This CCK-opioid interaction — the well-characterized antagonism between CCK2 signaling and endogenous opioid analgesia — positions GB-115 as a tool compound for dissecting spinal pain modulation circuits.
Cortisol/DHEA-S Axis Modulation
In rhesus monkey stress studies, GB-115 at 0.002 g reduced the cortisol/DHEA-S ratio — a neuroendocrine marker of HPA axis reactivity — without the global cortisol suppression produced by phenazepam. This indicates a more selective stress axis effect, potentially mediated through CCK-CRH pathway interactions.
Key Features & Specifications
GB-115 is provided as an encapsulated compound for CCK receptor pharmacology and anxiety research:
Chemical Analysis
| Property | Specification Reference Data |
|---|---|
| IUPAC Name | N-[2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-6-phenylhexanamide |
| CAS Number | 678996-63-9 |
| Molecular Formula | C25H30N4O3 |
| Molecular Weight | 434.5 g/mol |
| PubChem CID | 11281948 |
| DrugBank ID | DB19204 |
| Synonyms | Ranquilon; GB115; N-(1-oxo-6-phenylhexyl)glycyl-L-tryptophanamide; talanax |
| Form / Variation | Capsules (SKU C-056, $54.00) |
Storage, Safety, and Handling
Storage Protocol
Store capsules at 2–8 °C in a cool, dry environment protected from light. For solution preparation, GB-115 dissolves in polar organic solvents; aqueous solubility should be confirmed for each formulation. No standardized in vitro toxicity profile has been published; treat as an investigational laboratory compound with standard handling precautions.
Handling & Compliance
Handle with standard PPE. GB-115 is an investigational drug in Phase 2 clinical evaluation (NCT05586789) and has no approved therapeutic indication outside Russia, where early clinical studies originated. It is not currently listed as a WADA-prohibited substance or a scheduled controlled substance in the US. Institutional research ethics review is recommended for any clinical-adjacent protocol.