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Metabolism of a New Dipeptide Neuroprotector in Rats.

G B Kolyvanov1, P O Bochkov1, A A Litvin2

  • 1Laboratory of Pharmacokinetics, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.

Bulletin of Experimental Biology and Medicine
|March 30, 2022
PubMed
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N-Isocaproyl-L-Arginylglycine Hexamethylenediamide, First Low-Molecular-Weight Mimetic of Neurotrophin-4: Design and Neuroprotective Activity.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections·2026
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Transtraumatic Epidural Electrostimulation Promotes the Preservation of the Spinal Cord and Skeletal Muscles in Pigs.

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Relationship of the <i>1846G</i> > <i>A</i> Polymorphism of the <i>CYP2D6</i> Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis.

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Relationship of <i>CYP3A4*1B</i> Single Nucleotide Polymorphism to the Efficiency and Safety Profiles of Haloperidol in Patients Enduring Acute Alcoholic Hallucinosis.

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Preclinical Pharmacokinetics of GZK-111, a Dipeptide with Neuroprotective Activity.

Bulletin of experimental biology and medicine·2022

The metabolism of neuroprotector GZK-111 in rat blood plasma was studied. Key findings reveal ester bond hydrolysis and degradation pathways, yielding active compounds like cycloprolylglycine.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Neuroscience

Background:

  • The neuroprotector GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester) is a novel compound with potential therapeutic applications.
  • Understanding the metabolic fate of GZK-111 is crucial for evaluating its efficacy and safety profile.

Purpose of the Study:

  • To investigate the metabolic pathways of GZK-111 in rat blood plasma.
  • To identify the biotransformation products of GZK-111.

Main Methods:

  • High-Performance Liquid Chromatography (HPLC) coupled with mass spectrometry was employed.
  • Analysis of rat blood plasma samples incubated with GZK-111.

Main Results:

  • Four distinct biotransformation products of GZK-111 were identified.
Keywords:
GZK-111HPLC-mass spectrometrymetabolismneuroprotector

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  • The primary metabolic routes involve ester bond hydrolysis by esterases.
  • Further degradation leads to the formation of phenylacetic acid and cycloprolylglycine.

    • Conclusions:

    • GZK-111 undergoes significant biotransformation in rat blood plasma.
    • Hydrolysis of the ester bond is a major metabolic pathway.
    • The identified metabolite cycloprolylglycine possesses potential neuropsychotropic activity, warranting further investigation.