GB-115 vs NNZ-2591
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Ranquilon, N-phenylacetyl-L-prolylglycine ethyl ester
GB-115 is a synthetic dipeptide anxiolytic developed in Russia, chemically the amide of N-phenylhexanoyl-glycyl-L-tryptophan and described as a retro-analogue of cholecystokinin-4. Rather than acting like a benzodiazepine, it blocks cholecystokinin receptors, a different anti-anxiety route. It has been studied in animals and in a small pilot human study, but it is not an approved or widely available medication.
Also: Cyclo-L-glycyl-L-2-allylproline, Cyclic glycine-proline analog
NNZ-2591 is Neuren Pharmaceuticals' second drug, a synthetic analog of cyclic glycine-proline (cGP), a small ring-shaped molecule the body makes when it breaks down IGF-1. It is taken by mouth and is being developed for rare childhood neurodevelopmental disorders: Phelan-McDermid syndrome is furthest along, with the first-ever phase 3 trial in that disease started in late 2025, and Angelman and Pitt Hopkins syndromes behind it. Phase 2 results looked encouraging, but they were small open-label studies, so nobody knows yet whether it truly works.
Key Comparison Insights
- Both peptides belong to the Cognitive category, suggesting similar primary applications.
Detailed Comparison
| Attribute | GB-115 | NNZ-2591 |
|---|---|---|
| Category | Cognitive | Cognitive |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | Cholecystokinin (CCK) is a peptide that acts as a neurotransmitter in the brain, and activating its CCK-2 (also called CCK-B) and CCK-1 receptors tends to trigger anxiety and panic-like states. GB-115 works as an antagonist at these cholecystokinin receptors, meaning it occupies the receptor and blocks CCK from setting off that anxiety signaling. In animal work it specifically prevented anxiety provoked by CCK-4, which shares a pharmacological target with GB-115. This CCK-blocking mechanism is the proposed explanation for its calming effect, and it is distinct from the GABA system that classic sedatives act on. | Cyclic glycine-proline is thought to fine-tune IGF-1 activity in the brain by changing how IGF-1 binds to its carrier protein IGFBP-3. A 2014 Scientific Reports study proposed that cGP nudges IGF-1 activity up when it is low and down when it is high, a normalizing effect rather than a simple boost. NNZ-2591 adds an allyl group to the proline ring, making it resistant to enzymes and able to reach the brain after oral dosing. Trial protocols also describe reduced neuroinflammation and support for synapse function in animal models. It is a close cousin of trofinetide in spirit (both are small IGF-1-derived molecules from the same company), but the exact way it helps in these genetic syndromes has not been pinned down in humans. |
| Common Dosing | 6 mg daily (2 mg three times daily) 2-3 times daily (morning, afternoon, evening) | 12 mg/kg twice daily (phase 2 target trial dose) Twice daily |
| Administration | Oral tablets or sublingual | Oral liquid |
| Typical Duration | 21+ days in clinical trials, effects noted by day 7 | 13 weeks in phase 2 and phase 3 trials, with 12-month open-label extensions |
| Best Time to Take | Morning and throughout the day | Twice daily (trial schedule) |
Possible Side Effects May vary by individual |
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| Research Summary | The research record is real but thin and almost entirely from a single Russian group. In rodent studies (rats, BALB/c and C57Bl/6 mice), GB-115 reduced anxiety induced by CCK-4 and by yohimbine, with effects that varied by mouse strain, and it stayed effective after long-term dosing without producing tolerance or a withdrawal syndrome when stopped. Preclinical safety work has also been published. The only human data comes from a small pilot clinical study of 25 patients with generalized anxiety disorder given 6 mg daily for 21 days, where anxiety scores on the Hamilton scale fell substantially and fatigue scores improved. Importantly, that study was a single-arm pilot with no placebo or control group, so it cannot prove the drug caused the improvement. There are no large randomized controlled trials, no Western regulatory approval, and the evidence base remains preliminary. | The human data so far come from three small, open-label phase 2 trials of 13 weeks each, all with twice-daily oral dosing titrated up to a target of 12 mg/kg. In Phelan-McDermid syndrome (18 children, published in Neurology Genetics in 2026), 10 of 14 efficacy measures improved significantly from baseline, including clinician and caregiver global ratings, behavior, sleep and communication, and the drug was well tolerated with mostly mild to moderate side effects. Angelman syndrome (reported August 2024) showed a mean CGI-I of 3.0, with 11 of 13 children rated improved by clinicians. Pitt Hopkins syndrome (reported May 2024) showed improvement in 6 of 11 children on clinician-rated severity. The big caveat: none of these had a placebo group, and rare-disease trials with caregiver-rated outcomes are especially prone to placebo effects. A planned Prader-Willi trial was withdrawn before enrolling anyone. The real test is Koala, a randomized, double-blind, placebo-controlled phase 3 trial in about 160 children aged 3 to 12 with Phelan-McDermid syndrome (first patient dosed February 2026; estimated primary completion late 2027), with an open-label extension started in 2026. The FDA has given the program Fast Track, Rare Pediatric Disease and Orphan Drug designations. Neuren has also started work in neonatal hypoxic-ischemic encephalopathy, which is still preclinical. |
Frequently Asked Questions: GB-115 vs NNZ-2591
What is the difference between GB-115 and NNZ-2591?
GB-115 is a cognitive peptide that gb-115 is a synthetic dipeptide anxiolytic developed in russia, chemically the amide of n-phenylhexanoyl-glycyl-l-tryptophan and described as a retro-analogue of cholecystokinin-4. rather than acting like a benzodiazepine, it blocks cholecystokinin receptors, a different anti-anxiety route. it has been studied in animals and in a small pilot human study, but it is not an approved or widely available medication. NNZ-2591 is a cognitive peptide that nnz-2591 is neuren pharmaceuticals' second drug, a synthetic analog of cyclic glycine-proline (cgp), a small ring-shaped molecule the body makes when it breaks down igf-1. it is taken by mouth and is being developed for rare childhood neurodevelopmental disorders: phelan-mcdermid syndrome is furthest along, with the first-ever phase 3 trial in that disease started in late 2025, and angelman and pitt hopkins syndromes behind it. phase 2 results looked encouraging, but they were small open-label studies, so nobody knows yet whether it truly works. The main differences lie in their mechanisms of action and clinical applications.
Which is better, GB-115 or NNZ-2591?
Neither is universally "better" - the choice depends on your specific goals. GB-115 is typically used for cognitive purposes, while NNZ-2591 is used for cognitive. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can GB-115 and NNZ-2591 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using GB-115 and NNZ-2591 together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.