GL-II-73
GL-II-73 is a selective, orally active and blood-brain barrier permeable positive allosteric modulator of α5GABAA receptor, acting on the benzodiazepine-binding site of GABAA receptors. The binding selectivity of GL-II-73 for the α5 subtype is 6-, 11- and 12.5-fold higher than that for the α2, α1 and α3 subtypes, respectively. GL-II-73 reverses pilocarpine-induced hyperactivation of dopamine neurons in the ventral tegmental area, improves working memory and pyramidal neuron dendritic morphology in 5xFAD mice, but does not reduce β-amyloid load. GL-II-73 can be used in research related to Alzheimer's disease and temporal lobe epilepsy with comorbid psychosis.
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- CAS No.: 2133456-91-2
- Formule: C23H19FN4O
- Masse moléculaire:386.42
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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α5GABAA receptor |
GL-II-73 shows pH-dependent aqueous solubility, highest oil solubility in MCT, and excellent solubility in polar organic solvents including methanol and benzyl alcohol[1].
GL-II-73 (0.2% (w/w); 1 year) loaded nanoemulsion (NE4) maintains stable physicochemical properties suitable for parenteral administration for 1 year, with high encapsulation efficacy and GL-II-73 localized in the stabilizing layer near the aqueous phase[1].
GL-II-73 is a selective positive allosteric modulator of α5GABAₐRs, with 6-, 11-, and 12.5-fold higher affinity for α5 relative to α2, α1, and α3 GABAₐ receptor subunits, respectively[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Acute GL-II-73 (5-10 mg/kg; i.p.; single dose) administration reverses spatial working memory deficits in 2-month-old 5xFAD mice with early β-amyloid pathology[2].
Acute GL-II-73 (10 mg/kg; i.p.; single dose) administration produces a non-significant reversal of spatial working memory deficits in 5-month-old 5xFAD mice with late β-amyloid pathology, with alternation rates not differing from either WT controls or vehicle-treated 5xFAD mice[2].
Chronic GL-II-73 (30 mg/kg; p.o.; daily; 4 weeks) administration prevents spatial working memory deficits and fully reverses pyramidal neuron spine loss and dendritic shrinkage in 2-month-old 5xFAD mice with early β-amyloid pathology, independent of β-amyloid load[2].
GL-II-73 (75 ng; intra-vHipp; single administration) fully reverses pilocarpine-induced increases in VTA dopamine neuron population activity in a rat model of temporal lobe epilepsy[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5xFAD heterozygous and wild-type (WT) littermate mice (48% female, 2-month-old, Alzheimer's disease model with constitutive β-amyloid plaque accumulation)[2]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.p.; single dose
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Result:Reversed spatial working memory alternation rate deficits to levels indistinguishable from WT control mice in a dose-dependent manner.
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Animal Model:5xFAD heterozygous and wild-type (WT) littermate mice (50% female, 5-month-old, Alzheimer's disease model with constitutive β-amyloid plaque accumulation)[2]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.p.; single dose
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Result:Produced a non-significant reversal effect on spatial working memory alternation rates at 10 mg/kg, with rates not statistically different from either vehicle-treated 5xFAD mice or WT controls.
Failed to produce a meaningful reversal effect at 5 mg/kg.
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Animal Model:5xFAD heterozygous and wild-type (WT) littermate mice (50% female, 2-month-old, Alzheimer's disease model with constitutive β-amyloid plaque accumulation)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Restored spatial working memory alternation rates to levels indistinguishable from WT controls.
Completely reversed reduced apical and basal spine density, spine count, and dendritic length in prefrontal cortex (PFC) and hippocampal CA1 region to levels matching WT mice.
Reversed reduced density of nearly all spine maturation subtypes in both PFC and hippocampal CA1 region.
Showed no effect on β-amyloid plaque density in 5xFAD mice.
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Animal Model:5xFAD heterozygous and wild-type (WT) littermate mice (50% female, 5-month-old, Alzheimer's disease model with constitutive β-amyloid plaque accumulation)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Reversed spatial working memory alternation rate deficits to levels matching WT controls.
Significantly reversed reduced apical and basal spine density, spine count, and dendritic length in PFC and hippocampal CA1 region, though spine density remained statistically lower than WT levels.
Reversed reduced density of nearly all spine maturation subtypes in both PFC and hippocampal CA1 region.
Showed no effect on β-amyloid plaque density in 5xFAD mice.
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Animal Model:Sprague Dawley (adult male and female, 250-300 g, unilateral intra-ventral hippocampus injection of pilocarpine to induce status epilepticus and spontaneous recurrent seizures)[3]
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Dosage:75 ng
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Administration:intra-vHipp; single administration
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Result:Completely reversed the pilocarpine-induced increase in VTA dopamine neuron population activity, reducing the number of spontaneously active dopamine cells per track from 1.88 to 1.30.
Had no effect on VTA dopamine neuron population activity in saline-treated rats.
Did not alter average firing rate or percent burst firing in either pilocarpine- or saline-treated rats.
Chemical Information
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CAS No. 2133456-91-2
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Masse moléculaire 386.42
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Formule C23H19FN4O
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SMILES
O=C(C1=C2N(C=N1)C3=CC=C(C#C)C=C3C(C4=CC=CC=C4F)=N[C@@H]2C)N(C)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1].
Jezdić K, Đoković J, Jančić I, et al. Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain—Comparative In Vitro Blood-Brain Barrier and In Vivo Neuropharmacokinetic Evaluation. Pharmaceutics. 2025;17:354.
[Content Brief]
[2]. Bernardo AM, et al. Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer's disease pathology. Neurobiology of aging. 2025 Mar;147:49-59. [Content Brief]
[3]. McCoy AM, Prevot TD, Sharmin D, Cook JM, Sibille EL, Lodge DJ. GL-II-73, a Positive Allosteric Modulator of α5GABAA Receptors, Reverses Dopamine System Dysfunction Associated with Pilocarpine-Induced Temporal Lobe Epilepsy. Int J Mol Sci. 2023;24:11588. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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