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dipeptide

Glycyl-Glutamine

Published evidence · coverage incomplete

Anatomy in the research

Anatomy evidence is still being assembled.

These are anatomical mentions in cited research—not established treatment targets or proof of benefit in people.

This publication has no anatomy passages that meet our source-linking checks yet. Read the available findings ↓

General anatomy view only. No peptide-specific structures are highlighted.

At a glance

What is it—and why does it matter?

Oxidative stress and apoptosis readouts were analyzed, and the role of sigma receptor ligands was investigated as a possible mechanism. Using a model with subcutaneously implanted morphine pellets and naloxone-induced withdrawal, glycyl-glutamine administration 5 min prior to naloxone reduced withdrawal symptoms.

Sources for this introduction: [1] [2]

This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.

What is it?

A molecule, not a product name.

Identity

Glycyl-glutamine is an endogenous dipeptide identified as beta-endorphin(30-31), described here as being synthesized from beta-endorphin(1-31).

Molecular / pharmacology evidence

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide synthesized from beta-endorphin(1-31).

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Identity

Gly-Gln is a dipeptide; prior work has primarily treated it as a glutamine-donating compound.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Although the Glycyl-Glutamine (Gly-Gln) dipeptide has primarily been investigated as a glutamine donor, its direct pharmacological effects and underlying mechanisms remain poorly defined.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · BACKGROUND

    pubmed:42288053:7b80281c0d44:7b80281c0d44

How does it work?

Target, response, and disposition.

Mechanism

The study evaluated Gly-Gln in an in vitro cerebral ischemia-reperfusion injury model, measuring tissue viability and biochemical parameters.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    In this study, the effects of Gly-Gln on tissue viability and biochemical parameters were investigated using an in vitro model of cerebral ischemia-reperfusion injury.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · METHODS

    pubmed:42288053:7b80281c0d44:7b80281c0d44

Mechanism

Oxidative stress and apoptosis readouts were analyzed, and the role of sigma receptor ligands was investigated as a possible mechanism.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Oxidative stress and apoptotic markers were analyzed, and the potential involvement of sigma receptor ligands was examined.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · METHODS

    pubmed:42288053:7b80281c0d44:7b80281c0d44

Mechanism

In vitro, glutamine is reported to have stimulatory effects on lymphocytes and mucosa cells.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glutamine has stimulatory effects on lymphocytes and mucosa cells in vitro

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · OBJECTIVE

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Mechanism

The source states that Gly-Gln’s direct pharmacology and mechanisms have not been clearly established.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Although the Glycyl-Glutamine (Gly-Gln) dipeptide has primarily been investigated as a glutamine donor, its direct pharmacological effects and underlying mechanisms remain poorly defined.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · BACKGROUND

    pubmed:42288053:7b80281c0d44:7b80281c0d44

Pharmacokinetics

During GLY-GLN infusion, urinary losses of the dipeptide (GLY-GLN) and its constituent amino acids (GLN, GLY) were reported as negligible.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Excretion of GLY-GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible.

    Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients. · Abstract

    pubmed:8956477:14108385afb2:14108385afb2

What has been studied?

What the evidence says.

Comparative evidence

To test specificity, the study compared Gly-Gln with equimolar amounts of its degradation products (glycine and glutamine).

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    To assess whether the observed effects were specific to the dipeptide, equimolar concentrations of its degradation products, glycine and glutamine, were also evaluated.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · METHODS

    pubmed:42288053:7b80281c0d44:7b80281c0d44

Comparative evidence

A randomized controlled comparison in adults (15 per group) tested whether adding the dipeptides glycyl-glutamine/glycyl-tyrosine to an IV amino acid solution affected plasma and CSF measurements during a 12-hour preoperative infusion.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Cerebrospinal fluid (CSF) and plasma amino acid concentrations after administration of a glycyl‐glutamine/glycyltyrosine supplemented amino acid solution were therefore evaluated in a randomized controlled comparison with a conventional amino acid infusion.

    Cerebrospinal and Plasma Amino Acid Concentrations After Administration of IV Glycyl‐Glutamine and Glycyl‐Tyrosine Containing Amino Acid Solutions in Humans · Abstract

    doi:10.1177/0148607196020004281:fd4db3d517e6:fd4db3d517e6

Comparative evidence

The study included a control group of polytraumatized patients who received the parenteral nutrition solution without GLY-GLN supplementation.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Seven polytraumatized patients receiving the nutrition solution without GLY-GLN supplementation served as controls.

    Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients. · Abstract

    pubmed:8956477:14108385afb2:14108385afb2

Study findings

In a dependence paradigm evaluated via naloxone-precipitated withdrawal symptoms, administering glycyl-glutamine twice daily immediately before morphine (10 mg/kg i.p.) inhibited the development of morphine dependence in rats.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.)

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

In evaluated chemotherapy cycles, the glutamine group had a shorter median neutropenia duration (18 d) than control (22.5 d), with P = 0.052.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    The median durations of neutropenia were 18 d (range, 9-29 d) in the glutamine group and 22.5 d (range, 13-48 d) in the control group (P = 0.052)

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · RESULTS

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Study findings

In this model, ischemia-reperfusion increased oxidative damage and shifted antioxidant status: malondialdehyde rose and glutathione fell.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Ischemia-reperfusion significantly increased lipid peroxidation and disrupted antioxidant balance, as evidenced by elevated malondialdehyde levels and reduced glutathione content.

    Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors. · RESULTS

    pubmed:42288053:7b80281c0d44:7b80281c0d44

Study findings

In the authors’ conclusion, glutamine dipeptide–supplemented parenteral nutrition (GLN-PN) was described as reducing hospital length of stay and postoperative infectious-complication morbidity in postoperative patients.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    GLN-PN was beneficial to postoperative patients by shortening the length of hospital stay and reducing the morbidity of postoperative infectious complications.

    The impact of glutamine dipeptide-supplemented parenteral nutrition on outcomes of surgical patients: a meta-analysis of randomized clinical trials. · CONCLUSION

    pubmed:20852180:f01c9247b1d1:f01c9247b1d1

Study findings

Using a model with subcutaneously implanted morphine pellets and naloxone-induced withdrawal, glycyl-glutamine administration 5 min prior to naloxone reduced withdrawal symptoms.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone.

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

In conscious rats, a hemorrhage protocol of 2.5 ml/100 g body weight over 20 minutes reduced arterial pressure from 120.1 ± 2.9 to 56.2 ± 4.7 mmHg.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 ± 2.9 to 56.2 ± 4.7 mmHg)

    Glycyl-<scp>l</scp>-glutamine [β-endorphin-(30—31)] attenuates hemorrhagic hypotension in conscious rats · Abstract

    doi:10.1152/ajpregu.1997.273.5.r1598:8599de8abe88:8599de8abe88

Study findings

In evaluated chemotherapy cycles, median neutropenic fever duration was similar between glutamine (5.5 d) and control (5 d), P = 0.74.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    the median durations of neutropenic fever were 5.5 d (range, 0-13 d) and 5 d (range, 0-31 d), respectively (P = 0.74)

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · RESULTS

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Study findings

The study design was randomized, double-blind, and controlled, comparing glutamine-free parenteral nutrition vs glycyl-glutamine–supplemented parenteral nutrition that contained 20 g of glutamine in adults with acute myeloid leukemia receiving myelosuppressive chemotherapy.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    A randomized, double-blind, controlled study compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine-supplemented parenteral nutrition (Glamin, Baxter, Erlangen, Germany) containing 20 g of glutamine in adult patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy.

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · METHODS

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Study findings

Using a rat conditioned place preference paradigm (morphine sulfate 2.5 mg/kg i.p. on alternate days for 6 days; test day 7), pretreatment with glycyl-glutamine delivered i.c.v. at 1-100 nmol significantly reduced acquisition of morphine-induced place preference.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly.

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

At 100 nmol delivered i.c.v., glycyl-glutamine prevented expression of an existing morphine conditioned place preference.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference,

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

Using Kaplan–Meier methods and controlling for chemotherapy type, a subgroup receiving a high-dose cytarabine regimen showed significantly faster neutrophil recovery with glutamine versus control (P = 0.040).

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    we found a significantly faster neutrophil recovery in patients receiving glutamine than in the control group (P = 0.040) in patients receiving a high-dose cytarabine regimen.

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · RESULTS

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Study findings

When administered intracerebroventricularly at 10 or 100 nmol in normotensive rats, Gly-Gln showed no effect on arterial pressure or heart rate.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats.

    Glycyl-<scp>l</scp>-glutamine [β-endorphin-(30—31)] attenuates hemorrhagic hypotension in conscious rats · Abstract

    doi:10.1152/ajpregu.1997.273.5.r1598:8599de8abe88:8599de8abe88

Study findings

At 100 nmol i.c.v., glycyl-glutamine pretreatment was reported to partially reverse already-established morphine tolerance (as assessed in the study’s tolerance paradigm).

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    and partially reversed pre-established tolerance.

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

Under a repeated morphine regimen (10 mg/kg i.p., twice daily for 7 days) with antinociception assessed by tail-flick, pretreatment with 100 nmol i.c.v. glycyl-glutamine significantly delayed the development of morphine antinociceptive tolerance.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Glycyl-glutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

CSF measurements indicated no detectable entry (by the assay used) of glycyl-glutamine into CSF during the dipeptide-containing infusion, with a stated detection limit under 5.0 nmol/mL.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    The dipeptide‐containing solution did not increase either dipeptide to detectable levels in the CSF (detection limit < 5.0 nmol/mL).

    Cerebrospinal and Plasma Amino Acid Concentrations After Administration of IV Glycyl‐Glutamine and Glycyl‐Tyrosine Containing Amino Acid Solutions in Humans · Abstract

    doi:10.1177/0148607196020004281:fd4db3d517e6:fd4db3d517e6

Study findings

In venous blood, the infusion containing glycyl-glutamine produced a measurable increase, reaching 308 ± 111 nmol/mL with statistical significance (p <.05).

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Venous glycyl‐glutamine increased from below detection limits up to 308 ± 111 nmol/mL (p <.05)

    Cerebrospinal and Plasma Amino Acid Concentrations After Administration of IV Glycyl‐Glutamine and Glycyl‐Tyrosine Containing Amino Acid Solutions in Humans · Abstract

    doi:10.1177/0148607196020004281:fd4db3d517e6:fd4db3d517e6

Study findings

At 100 nmol i.c.v., glycyl-glutamine was reported not to disrupt acquisition of conditioned place preference when the reward was palatable food.

Animal / laboratory evidence

1 cited source · Study independence not established

Animal or laboratory findings do not establish benefit or safety in people.

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    but it did not interfere with acquisition of a conditioned place preference to palatable food,

    Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. · Abstract

    pubmed:16079299:5e8bbb4b6efc:5e8bbb4b6efc

Study findings

A meta-analysis of randomized trials reported a reduction in hospital length of stay when glycyl-glutamine (a glutamine dipeptide) was used in parenteral nutrition compared with standard parenteral nutrition, quantified as a weighted mean difference (WMD) of -5.40 days with a 95% confidence interval of -8.46 to -2.33.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    Fourteen randomized controlled trials (RCTs) (N = 587) were included in this meta-analysis. The results showed that glutamine dipeptide significantly reduced the length of hospital stay by around 4 days in the form of alanyl-glutamine (weighted mean difference [WMD] = -3.84; 95% confidence interval [CI] -5.40, -2.28; z = 4.82; P < .001) and about 5 days in the form of glycyl-glutamine (WMD = -5.40; 95% CI -8.46, -2.33; z = 3.45; P < .001).

    The impact of glutamine dipeptide-supplemented parenteral nutrition on outcomes of surgical patients: a meta-analysis of randomized clinical trials. · RESULTS

    pubmed:20852180:f01c9247b1d1:f01c9247b1d1

Study findings

Pooling randomized trials, GLN-PN (parenteral nutrition supplemented with glutamine dipeptide) was associated with a lower rate of infectious complications compared with standard PN, reported as a risk ratio of 0.69 (95% CI 0.50 to 0.95).

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    The overall effect indicated a significant decrease in the infectious complication rates of surgical patients receiving GLN-PN (risk ratio = 0.69; 95% CI 0.50, 0.95; z = 2.26; P = .02).

    The impact of glutamine dipeptide-supplemented parenteral nutrition on outcomes of surgical patients: a meta-analysis of randomized clinical trials. · RESULTS

    pubmed:20852180:f01c9247b1d1:f01c9247b1d1

Study findings

Measured immune cell recovery (CD4+, CD8+) and monocyte activation showed no significant between-group differences.

Human research · design must be checked

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    There was no significant difference in the recovery of CD4+ or CD8+ lymphocytes or monocyte activation between groups.

    Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. · RESULTS

    pubmed:14990264:9a916ba15bde:9a916ba15bde

Risks and interactions

Risks, organized for scanning.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Products and regulatory status

Same ingredient. Different records.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Administration context

The practical clinical context.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Additional research & classification gaps

4 archived statements are kept separate from drug-effect findings. Media studies, economic models, methods, and records with unresolved scope are not used as medical-effect evidence.

Inspect contextual research (4)
Research context · scope unclassified

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

The abstract’s overall conclusion is that glycyl-glutamine reduces multiple morphine-induced adaptations (conditioned place preference, tolerance, dependence, withdrawal) while not compromising morphine analgesia.

Research context only—not evidence of a treatment effect.

Research context · scope unclassified

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

In a pig small-bowel autotransplant model, adding the dipeptide glycyl-glutamine to long-term TPN was associated with higher graft mucosal glutamine (Gln) and protein content compared with standard TPN.

Research context only—not evidence of a treatment effect.

Research context · scope unclassified

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

Gly-Gln is identified as a dipeptide (glycine + glutamine) and is stated to be a stable form of glutamine (Gln).

Research context only—not evidence of a treatment effect.

Research context · scope unclassified

1 cited source · Study independence not established

How to read this evidence

Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.

1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.

The source states that free Gln has two limitations: poor stability and low small-intestinal absorption.

Research context only—not evidence of a treatment effect.

Research status + gaps

What still needs better answers?

  • No publishable claim yet for: administration, contraindication, interaction, regulatory, safety
  • 58 compiled claim(s) withheld by automated assurance: assurance_score_below_0.58 (36), assurance_score_below_0.72 (14), current_regulatory_source_required (15), extraction_ambiguity (42), high_risk_requires_regulatory_or_two_independent_sources (20), no_direct_support (44), proposal_not_staged (3)

These are the limits of this profile, not an exhaustive list of scientific uncertainties.

References + discovery

Open the records yourself.

  1. Glycyl-<scp>l</scp>-glutamine [β-endorphin-(30—31)] attenuates hemorrhagic hypotension in conscious rats

    doi · published 1997-11-01 · retrieved 2026-09-04T19:33:53Z

  2. Cerebrospinal and Plasma Amino Acid Concentrations After Administration of IV Glycyl‐Glutamine and Glycyl‐Tyrosine Containing Amino Acid Solutions in Humans

    doi · published 1996-07-01 · retrieved 2026-09-04T19:33:54Z

  3. Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig.

    pubmed · published 2003-12-01 · retrieved 2026-09-08T21:49:20Z

  4. Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy.

    pubmed · published 2004-03-01 · retrieved 2026-09-08T21:49:22Z

  5. Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal.

    pubmed · published 2005-11-01 · retrieved 2026-09-04T19:33:54Z

  6. The impact of glutamine dipeptide-supplemented parenteral nutrition on outcomes of surgical patients: a meta-analysis of randomized clinical trials.

    pubmed · published 2010-01-01 · retrieved 2026-09-09T21:57:10Z

  7. Dietary Glycyl-Glutamine Supplementation Improves Growth, Immunity, Antioxidant Capacity, and Apparent Digestibility of Weaned Piglets.

    pubmed · published 2025-09-02 · retrieved 2026-08-27T11:48:55Z

  8. Protective Effects of Glycyl-Glutamine Dipeptide on In Vitro Brain Ischemia Reperfusion Model and the Role of Sigma-1 Receptors.

    pubmed · published 2026-06-13 · retrieved 2026-08-27T11:48:55Z

  9. Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients.

    pubmed · published 1996-01-01 · retrieved 2026-09-08T21:49:21Z

Publication history and provenance

Version 2 · Automated assessment · 2026-09-09T21:57:10Z

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